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<title>20 August, 2022</title>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion</strong> -
<div>
Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune responses, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform’s true impact on human health.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.03.16.484616v2" target="_blank">Pre-exposure to mRNA-LNP inhibits adaptive immune responses and alters innate immune fitness in an inheritable fashion</a>
</div></li>
<li><strong>Disrupted chromatin architecture in olfactory sensory neurons: A missing link from COVID-19 infection to anosmia</strong> -
<div>
We tackle here genomic mechanisms of a rapid onset and recovery from anosmia - a useful diagnostic indicator for early-stage COVID-19 infection. On the basis of earlier observed specifics of olfactory receptors (ORs) regulation in the mice chromatin structures, we hypothesized that the disruption of OR function can be caused by chromatin reorganization taking place upon SARS-CoV-2 infection. We reconstructed the chromatin ensembles of ORs obtained from COVID-19 patients and control samples using our original computational framework for the whole-genome chromatin ensemble 3D reconstruction. We have also developed here a new procedure for the analysis of fine structural hierarchy in local, megabase scale, parts of chromosomes containing the OR genes and corresponding epigenetic factors. We observed structural modifications in COVID-19 patients on different levels of chromatin organization, from alteration of the whole genome structure and chromosomal intermingling to reorganization of contacts between the chromatin loops at the level of topologically associating domains. While complementary data on known regulatory elements point to pathology-associated changes within the overall picture of chromatin alterations, further investigation using additional epigenetic factors mapped on 3D reconstructions with improved resolution will be required for better understanding of anosmia caused by SARS-CoV-2 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.19.504545v1" target="_blank">Disrupted chromatin architecture in olfactory sensory neurons: A missing link from COVID-19 infection to anosmia</a>
</div></li>
<li><strong>Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cells in recovered COVID-19 pregnant women</strong> -
<div>
Pregnancy is a complex phenomenon during which women undergo immense immunological change throughout this period. Having an infection with the SARS-CoV-2 virus leads to an additional burden on the highly stretched immune response. Some studies suggest that age-matched pregnant women are more prone to SARS-CoV-2 infection compared with normal healthy (non-pregnant) women, while alternative evidence proposed that pregnant women are neither susceptible nor develop severe symptoms. This discrepancy in different findings regarding the immune responses of pregnant women infected with the SARS-CoV-2 virus is not well understood. In this study, we investigated how SARS-CoV-2 viral infection could modulate the immune landscape during the active infection phase and recovery in pregnant females. Using flow cytometry, we identified that intermediate effector CD8+ T cells were increased in pregnant women who had recovered from COVID-19 as opposed to those currently infected. Similarly, an increase in CD4+ T helper cells (early or late) during the recovered phase was observed during the recovery phase compared with infected pregnant women or healthy pregnant women, whilst infected pregnant women had a reduced number of late effector CD4+ T cells. CD3+CD4-CD8-NKT cells that diminished during active infection in contrast to healthy pregnant women were a significant increase in recovered COVID-19 recovered pregnant women. Further, our single-cell RNA sequencing data revealed that infection of SARS-CoV-2 had changed the gene expression profile of monocytes, CD4+ effector cells and antibody-producing B cells in convalescent as opposed to healthy pregnant women. Additionally, several genes with cytotoxic function, interferon signalling type I &amp; II, and pro- and anti-inflammatory functions in natural killer cells and CD8+ cytotoxic T cells were compromised in recovered patients compared with healthy pregnant women. Overall, our study highlights that SARS-CoV-2 infection deranged the adaptive immune response in pregnant women and could be implicated in pregnancy complications in ongoing pregnancies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.18.504053v1" target="_blank">Single-cell RNA sequencing highlights a reduced function of natural killer and cytotoxic T cells in recovered COVID-19 pregnant women</a>
</div></li>
<li><strong>Within-host genetic diversity of SARS-CoV-2 in the context of large-scale hospital-associated genomic surveillance</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The COVID-19 pandemic has resulted in extensive surveillance of the genomic diversity of SARS-CoV-2. Sequencing data generated as part of these efforts can also capture the diversity of the SARS-CoV-2 virus populations replicating within infected individuals. To assess this within-host diversity of SARS-CoV-2 we quantified low frequency (minor) variants from deep sequence data of thousands of clinical samples collected by a large urban hospital system over the course of a year. Using a robust analytical pipeline to control for technical artefacts, we observe that at comparable viral loads, specimens from patients hospitalized due to COVID-19 had a greater number of minor variants than samples from outpatients. Since individuals with highly diverse viral populations could be disproportionate drivers of new viral lineages in the patient population, these results suggest that transmission control should pay special attention to patients with severe or protracted disease to prevent the spread of novel variants.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.17.22278898v1" target="_blank">Within-host genetic diversity of SARS-CoV-2 in the context of large-scale hospital-associated genomic surveillance</a>
</div></li>
<li><strong>Relative contributions of vaccination and previous infection to population-level SARS-CoV-2 immunity over time: a simulation modelling study</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Population-level immunity to SARS-CoV-2 directly impacts the incidence of COVID-19 morbidity and mortality. Understanding how this immunity is likely to change over time in the context of future vaccination schedules and emerging SARS-CoV-2 variants is critical to inform pandemic policy. This study simulates population-level COVID-19 immunity (including relative contributions of vaccination and previous infection) in Victoria, Australia over 18 months using an agent-based model and logistic regression equations that predict immunity and waning following vaccination and/or infection. Previous infection was found to drive most immunity against infection even with ongoing regular vaccination, however a greater proportion of overall immunity against mortality was accounted for by vaccination. Although previous infection appears to be driving a substantial component of population-level COVID-19 immunity currently, improved vaccines providing longer lasting (and better sterilizing) immunity are likely to be a critical component of the future pandemic response given the risks associated with SARS-CoV-2 infection.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.18.22278963v1" target="_blank">Relative contributions of vaccination and previous infection to population-level SARS-CoV-2 immunity over time: a simulation modelling study</a>
</div></li>
<li><strong>Demographic and Outcome Characteristics of Children Hospitalized with Acute COVID-19 versus Multisystem Inflammatory Syndrome in Children in Canada</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Direct comparisons of pediatric hospitalizations for acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) can inform health system planning. While there were more hospitalizations and deaths from acute COVID-19 amongst Canadian children between March 2020-May 2021, MIS-C cases were more severe, requiring more intensive care and vasopressor support.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.08.18.22278939v1" target="_blank">Demographic and Outcome Characteristics of Children Hospitalized with Acute COVID-19 versus Multisystem Inflammatory Syndrome in Children in Canada</a>
</div></li>
<li><strong>Loss of Control Eating and COVID 19 Factors</strong> -
<div>
Loss-of-control eating (LOCE) is the perceived inability to stop eating once one has started or feeling unable to resist eating onset. LOCE has been found to be highly driven by mood, and particularly negative mood. However, it has been indicated that LOCE pathology increased during the coronavirus disease 2019 (COVID-19) pandemic, evincing a need to understand the unique factors and concerns that may contribute to LOCE during COVID-19. Given that COVID-19 has also been associated with significant increase in stressors across multiple domains, such as fear of contracting the virus, an effect exists of the pandemic on both positive and negative mood, and those fears could arguably in turn effect a relationship between mood and LOCE. In addition, it was hypothesized that daily protective strategies meant to prevent contagion may be associated with LOCE. A sample of n = 109 adults from the United States completed an online diary study over the course of ten days regarding their daily LOCE, positive and negative mood, and protective behaviors against contagion. Data were analyzed both within- and between-subjects with a Bayesian method to examine the direct relationships between predictors and LOCE. Participants indicated their illness fear beliefs at a baseline assessment, which was hypothesized to predict LOCE directly between subjects and have a cross-level interactive effect on predictors within-subjects. Negative mood was associated with LOCE at both levels, and positive mood and protective behaviors did not reveal significant direct associations with LOCE, nor did illness fear beliefs. However, an interactive effect between illness fear beliefs and with within-subject positive mood was found, such that when illness fear beliefs were low, positive mood had a significant inverse association with LOCE. Findings and implications are discussed.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/ta659/" target="_blank">Loss of Control Eating and COVID 19 Factors</a>
</div></li>
<li><strong>Pandemic-Related Changes in the Prevalence of Early Adolescent Alcohol and Drug Use, 2020-2021: A Multisite, Longitudinal, Prospective Cohort Study</strong> -
<div>
Purpose: Evaluate changes in early adolescent substance use from May 2020 to May 2021 during the coronavirus disease 2019 (COVID-19) pandemic using a prospective, longitudinal, nationwide cohort: the Adolescent Brain Cognitive DevelopmentSM Study. Method: 9,270 youth ages 11-12 years old completed up to seven assessments between May 2020 and May 2021, reporting on past-month use of alcohol and drugs. The prevalence of use was compared to that at pre-pandemic assessments completed in 2018-2019, adjusting for the age-related increases in substance use expected over time. Results: Pandemic-related decreases in the prevalence of alcohol use were detectable in May 2020, grew larger over time, and remained substantial in May 2021 (0.3% vs. 3.2% pre- pandemic, p&lt;.001). Pandemic-related increases in inhalant use and prescription drug misuse were detectable in May 2020, shrunk over time, and were smaller but still detectable in May 2021 (0.2% vs. 0% pre-pandemic, p&lt;.001). Pandemic-related increases in nicotine use were detectable between May 2020 and March 2021 and no longer significantly different from pre- pandemic levels in May 2021 (0.5% vs. 0.2% pre-pandemic, p=.09). There was significant heterogeneity in pandemic-related change in substance use at some timepoints, with increased rates among youth identified as Black or Hispanic or in lower-income families versus stable or decreased rates among youth identified as White or in higher-income families. Conclusions: Among 11-12 year-olds, rates of alcohol use remained dramatically reduced in May 2021 relative to pre-pandemic and rates of prescription drug misuse and inhalant use remained modestly increased. Differences remained despite partial restoration of pre-pandemic life, raising questions about whether youth who spent early adolescence under pandemic conditions may exhibit persistently different patterns of substance use.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/jhma5/" target="_blank">Pandemic-Related Changes in the Prevalence of Early Adolescent Alcohol and Drug Use, 2020-2021: A Multisite, Longitudinal, Prospective Cohort Study</a>
</div></li>
<li><strong>Public attitudes to social care in Wales following the COVID-19 pandemic</strong> -
<div>
Background. The COVID-19 pandemic has shone further light on some of the challenges facing social care in Wales, as in many countries, and looks to have exacerbated a crisis that was already extant. This has led to the intensification of longer-standing arguments that social reform is necessary and that the pandemic presents an added impetus and opportunity for reform. Methods. An online survey was completed by 2569 respondents between February 11th and March 11th, 2022. Additionally, online focus groups were conducted with a sample of 14 participants. The inclusion criteria were adults aged 18 years and over living in Wales. Results. Four-in-ten of those who felt that they or someone in their household or close family needed social care during the past two years did not receive or make use of it. The pandemic was cited as a major reason why many of those who may have needed social care didn’t access it Satisfaction with social care was variable, with approximately one-third either very or quite dissatisfied, and a little over half either very or quite satisfied with social care services for themselves or a household or close family member. Discussion. Social care policymakers and providers should seek to understand and address what people feel are the main barriers to accessing or using social care, including increasing provision for those who need it, encouraging and enabling those who feel they need social care to apply, consider broadening the eligibility criteria where appropriate, and simplifying the application process.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://psyarxiv.com/7jnca/" target="_blank">Public attitudes to social care in Wales following the COVID-19 pandemic</a>
</div></li>
<li><strong>Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape</strong> -
<div>
Consecutive waves of SARS-CoV-2 infection have been driven in part by the repeated emergence of variants with mutations that confer resistance to neutralizing antibodies Nevertheless, prolonged or repeated antigen exposure generates diverse memory B-cells that can produce affinity matured receptor binding domain (RBD)-specific antibodies that likely contribute to ongoing protection against severe disease. To determine how SARS-CoV-2 omicron variants might escape these broadly neutralizing antibodies, we subjected chimeric viruses encoding spike proteins from ancestral, BA.1 or BA.2 variants to selection pressure by a collection of 40 broadly neutralizing antibodies from individuals with various SARS-CoV-2 antigen exposures. Notably, pre-existing substitutions in the BA.1 and BA.2 spikes facilitated acquisition of resistance to many broadly neutralizing antibodies. Specifically, selection experiments identified numerous RBD substitutions that did not confer resistance to broadly neutralizing antibodies in the context of the ancestral Wuhan-Hu-1 spike sequence, but did so in the context of BA.1 and BA.2. A subset of these substitutions corresponds to those that have appeared in several BA.2 daughter lineages that have recently emerged, such as BA.5. By including as few as 2 or 3 of these additional changes in the context of BA.5, we generated spike proteins that were resistant to nearly all of the 40 broadly neutralizing antibodies and were poorly neutralized by plasma from most individuals. The emergence of omicron variants has therefore not only allowed SARS-CoV-2 escape from previously elicited neutralizing antibodies but also lowered the genetic barrier to the acquisition of resistance to the subset of antibodies that remained effective against early omicron variants.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.17.504313v1" target="_blank">Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape</a>
</div></li>
<li><strong>Ancestral lineage of SARS-CoV-2 is more stable in human biological fluids than Alpha, Beta and Omicron variants of concern</strong> -
<div>
SARS-CoV-2 is a zoonotic virus which was first identified in 2019, and has quickly spread worldwide. The virus is primarily transmitted through respiratory droplets from infected persons; however, the virus-laden excretions can contaminate surfaces which can serve as a potential source of infection. Since the beginning of the pandemic, SARS-CoV-2 has continued to evolve and accumulate mutations throughout its genome leading to the emergence of variants of concern (VOCs) which exhibit increased fitness, transmissibility, and/or virulence. However, the stability of SARS-CoV-2 VOCs in biological fluids has not been thoroughly investigated so far. The aim of this study was to determine and compare the stability of different SARS-CoV-2 strains in human biological fluids. Here, we demonstrate that the ancestral strain of Wuhan-like lineage A was more stable than the Alpha VOC B.1.1.7, and the Beta VOC B.1.351 strains in human liquid nasal mucus and sputum. In contrast, there was no difference in stability among the three strains in dried biological fluids. Furthermore, we also show that the Omicron VOC B.1.1.529 strain was less stable than the ancestral Wuhan-like strain in liquid nasal mucus. These studies provide insight into the effect of the molecular evolution of SARS-CoV-2 on environmental virus stability, which is important information for the development of countermeasures against SARS-CoV-2.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.17.504362v1" target="_blank">Ancestral lineage of SARS-CoV-2 is more stable in human biological fluids than Alpha, Beta and Omicron variants of concern</a>
</div></li>
<li><strong>Fertility recovery despite the COVID-19 pandemic in Finland?</strong> -
<div>
Finland’s increase in births, recorded in the months following the first two waves of the COVID-19 pandemic, was among the strongest. We assess whether the fertility increase in Finland occurred because of or despite the pandemic, or both, by investigating the country’s fertility trends by women’s region of residence, age group, and parity. While the country as a whole was modestly hit by the pandemic in 2020, the capital region Helsinki-Uusimaa faced more severe restrictions. We used aggregate register data until September 2021 to assess monthly fertility. In 2020 and 2021, the relative annual increases in fertility were strongest among women aged 30–34 and 35–49. In 2021, but not in 2020, fertility increased most in Helsinki-Uusimaa, and across all parities. Model-based estimates provided tentative support for an overall pandemic fertility boost for the time period until September 2019. We conclude that the unusual fertility increases in 2021 in Finland broadly follow from pre-existing trends where the country recovers from its all-time low fertility, but do not exclude the possibility of an additional boost from the pandemic itself. The study highlights the importance of carefully considering existing fertility trends when studying fertility responses to the pandemic.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/fxwe3/" target="_blank">Fertility recovery despite the COVID-19 pandemic in Finland?</a>
</div></li>
<li><strong>A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses</strong> -
<div>
Viruses are dependent on interactions with host factors in order to efficiently establish an infection and replicate. Targeting such interactions provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking, and has previously been shown to be important for HPV infection. Here we show that a highly potent and metabolically stable peptide inhibitor that binds to the PDZ1 domain of syntenin inhibits SARS-CoV-2 infection by blocking the endosomal entry of the virus. Furthermore, we found that the inhibitor also hampered chikungunya infection, and strongly reduced flavivirus infection, which are completely dependent on receptor mediated endocytosis for their entry. In conclusion, we have identified a novel pan-viral inhibitor that efficiently target a broad range of RNA viruses.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.18.504268v1" target="_blank">A syntenin inhibitor blocks endosomal entry of SARS-CoV-2 and a panel of RNA viruses</a>
</div></li>
<li><strong>SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model</strong> -
<div>
Despite being largely confined to the airways, SARS-CoV-2 infection has been associated with sensory abnormalities that manifest in both acute and long-lasting phenotypes. To gain insight on the molecular basis of these sensory abnormalities, we used the golden hamster infection model to characterize the effects of SARS-CoV-2 versus Influenza A virus (IAV) infection on the sensory nervous system. Efforts to detect the presence of virus in the cervical/thoracic spinal cord and dorsal root ganglia (DRGs) demonstrated detectable levels of SARS-CoV-2 by quantitative PCR and RNAscope uniquely within the first 24 hours of infection. SARS-CoV-2-infected hamsters demonstrated mechanical hypersensitivity during acute infection; intriguingly, this hypersensitivity was milder, but prolonged when compared to IAV-infected hamsters. RNA sequencing (RNA-seq) of thoracic DRGs from acute infection revealed predominantly neuron-biased signaling perturbations in SARS-CoV-2-infected animals as opposed to type I interferon signaling in tissue derived from IAV-infected animals. RNA-seq of 31dpi thoracic DRGs from SARS-CoV-2-infected animals highlighted a uniquely neuropathic transcriptomic landscape, which was consistent with substantial SARS-CoV-2-specific mechanical hypersensitivity at 28dpi. Ontology analysis of 1, 4, and 30dpi RNA-seq revealed novel targets for pain management, such as ILF3. Meta-analysis of all SARS-CoV-2 RNA-seq timepoints against preclinical pain model datasets highlighted both conserved and unique pro-nociceptive gene expression changes following infection. Overall, this work elucidates novel transcriptomic signatures triggered by SARS-CoV-2 that may underlie both short- and long-term sensory abnormalities while also highlighting several therapeutic targets for alleviation of infection-induced hypersensitivity.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.08.19.504551v1" target="_blank">SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model</a>
</div></li>
<li><strong>A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The unfolding of the COVID-19 pandemic has been very difficult to predict using mathematical models for infectious diseases. While it has been demonstrated that variations in susceptibility have a damping effect on key quantities such as the incidence peak, the herd-immunity threshold and the final size of the pandemic, this complex phenomenon is almost impossible to measure or quantify, and it remains unclear how to incorporate it for modeling and prediction. In this work we show that, from a modeling perspective, variability in susceptibility on an individual level is equivalent with a fraction theta of the population having an ``artificial99 sterilizing immunity. Given that this new parameter theta can be estimated, we also derive formulas for R0, the herd-immunity threshold and the final size of the pandemic. In the particular case of SARS-CoV-2, there is by now undoubtedly variable susceptibility due to waning immunity from both vaccines and previous infections, and our findings may be used to greatly simplify models. If such variations were also present prior to the first wave, as indicated by a number of studies, these findings can help explain why the magnitude of the initial waves of SARS-CoV-2 was relatively low, compared to what one may have expected based on standard models.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.08.21260175v2" target="_blank">A note on variable susceptibility, the herd-immunity threshold and modeling of infectious diseases</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Clinical Study to Evaluate the Efficacy and Safety of SIM0417 Orally Co-Administered With Ritonavir in Symptomatic Adult Participants With Mild to Moderate COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: SIM0417;   Drug: Placebo<br/><b>Sponsor</b>:   Jiangsu Simcere Pharmaceutical Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Self-management of Post COVID-19 Syndrome Using Wearable Biometric Technology</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Other: Self-management of post COVID-19 respiratory outcomes<br/><b>Sponsor</b>:   University of Manitoba<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Casirivimab and Imdevimab Drug Combination;   Drug: Remdesivir;   Drug: Favipiravir<br/><b>Sponsor</b>:   Mansoura University Hospital<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Role of BCG Vaccine in the Clinical Evolution of COVID-19 and in the Efficacy of Anti-SARS-CoV-2 Vaccines</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: BCG (Bacillus Calmette-Guérin) vaccine;   Other: Placebo<br/><b>Sponsors</b>:   Oswaldo Cruz Foundation;   University of Sao Paulo;   Federal University of Juiz de Fora<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation in Post-COVID-19 Condition</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: Goal Management Training (GMT)<br/><b>Sponsors</b>:   Lovisenberg Diakonale Hospital;   University of Oslo;   Icahn School of Medicine at Mount Sinai;   University of Toronto;   UiT The Arctic University of Norway;   Oslo University Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Performance Evaluation of LumiraDx COVID-19 (SARS-CoV-2) Ag ULTRA Test (ASPIRE-2)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Diagnostic Test: Nasal Swab;   Diagnostic Test: Nasopharyngeal swab<br/><b>Sponsor</b>:   LumiraDx UK Limited<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Social Network Diffusion of COVID-19 Prevention for Diverse Criminal Legal Involved Communities</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Other: Education;   Other: Motivational<br/><b>Sponsor</b>:   University of Chicago<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Booster Immunization With COVID-19 Vaccine,Inactivated Co -Administration With Influenza Vaccine and Pneumococcal Polysaccharide Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Biological: Adult group in immunogenicity and safety study of combined immunization;   Biological: Elderly group in immunogenicity and safety study of combined immunization;   Biological: Adult group in safety observation study of combined immunization;   Biological: Elderly group in safety observation study of combined immunization<br/><b>Sponsor</b>:   Sinovac Biotech Co., Ltd<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>EFFECTS OF INSPIRATORY MUSCLE TRAINING IN POST-COVID-19 PATIENTS</strong> - <b>Condition</b>:   Covid19<br/><b>Interventions</b>:   Other: TREATMENT GROUP (TG);   Other: CONTROL GROUP (CG)<br/><b>Sponsor</b>:   University Vila Velha<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long-term Effects of SARS-CoV-2 on the Central Nervous System and One-year Follow-up of “Long COVID-19” Patients</strong> - <b>Condition</b>:   Long Covid19<br/><b>Intervention</b>:   Diagnostic Test: Perfusion brain scintigraphy imaging<br/><b>Sponsor</b>:   Brugmann University Hospital<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With COVID-19</strong> - <b>Condition</b>:   COVID-19 Infection<br/><b>Interventions</b>:   Biological: Allogeneic umbilical cord mesenchymal stem cells;   Biological: Controlled normal saline<br/><b>Sponsor</b>:   Ever Supreme Bio Technology Co., Ltd.<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome</strong> - <b>Condition</b>:   Post-COVID-19 Syndrome<br/><b>Interventions</b>:   Drug: Temelimab 54mg/kg;   Drug: Placebo<br/><b>Sponsor</b>:   GeNeuro SA<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Active Cycle Of Breathing Technique Verses Breathing Exercises In Post ICU COVID-19 Patients</strong> - <b>Condition</b>:   Post Covid-19 Patients<br/><b>Interventions</b>:   Other: Chest physiotherapy with breathing exercises and ACBT;   Other: Chest physiotherapy with breathing exercises<br/><b>Sponsor</b>:   Riphah International University<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effects of a Sublingual Sprayable Microemulsion of Vitamin D on Inflammatory Markers in COVID-19 Patients</strong> - <b>Conditions</b>:   COVID-19;   Vitamin D Deficiency<br/><b>Intervention</b>:   Dietary Supplement: Vitamin D 25 (OH) 12000 IU in the form of a sublingual sprayable microemulsion<br/><b>Sponsor</b>:   Pauls Stradins Clinical University Hospital<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UNAIR Inactivated COVID-19 Vaccine Phase 3</strong> - <b>Conditions</b>:   COVID-19 Pandemic;   COVID-19 Vaccines<br/><b>Interventions</b>:   Biological: Vaksin Merah Putih - UA SARS-CoV-2 (Vero Cell Inactivated) 5 µg;   Biological: CoronaVac Biofarma COVID-19 Vaccine<br/><b>Sponsors</b>:   Dr. Soetomo General Hospital;   Indonesia-MoH;   Universitas Airlangga;   Biotis Pharmaceuticals, Indonesia<br/><b>Recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computational Design of Miniprotein Inhibitors Targeting SARS-CoV-2 Spike Protein</strong> - The ongoing pandemic of COVID-19 caused by SARS-CoV-2 has become a global health problem. There is an urgent need to develop therapeutic drugs, effective therapies, and vaccines to prevent the spread of the virus. The virus first enters the host cell through the interaction between the receptor binding domain (RBD) of spike protein and the peptidase domain (PD) of the angiotensin-converting enzyme 2 (ACE2). Therefore, blocking the binding of RBD and ACE2 is a promising strategy to inhibit the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In silico identification of novel SARS-CoV-2 main protease and non-structural protein 13 (nsp13) inhibitors through consensus docking and free binding energy calculations</strong> - CONCLUSION: In conclusion, the analysis of the results identified that the phytochemicals demonstrated enhanced binding capacities, compared to the FDA-approved database.
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"></p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Digging for the discovery of SARS-CoV-2 nsp12 inhibitors: a pharmacophore-based and molecular dynamics simulation study</strong> - Aim: COVID-19 is a global health threat. Therapeutics are urgently needed to cure patients severely infected with COVID-19. Objective: to investigate potential candidates of nsp12 inhibitors by searching for druggable cavity pockets within the viral protein and drug discovery. Methods: A virtual screening of ZINC natural products on SARS-CoV-2 nsp12’s druggable cavity was performed. A lead compound with the highest affinity to nsp12 was simulated dynamically for 10 ns. Results: ZINC03977803 was…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody feedback regulation of memory B cell development in SARS-CoV-2 mRNA vaccination</strong> - Feedback inhibition of humoral immunity by antibodies was initially documented in guinea pigs by Theobald Smith in 1909, who showed that passive administration of excess anti-Diphtheria toxin inhibited immune responses ¹ . Subsequent work documented that antibodies can enhance or inhibit immune responses depending on antibody isotype, affinity, the physical nature of the antigen, and engagement of immunoglobulin (Fc) and complement (C’) receptors ^(2, 3) . However, little is known about how…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized Trial of Lipid Metabolism Modulation with Fenofibrate for Acute Coronavirus Disease 2019</strong> - Background Abnormal cellular lipid metabolism appears to underlie SARS-CoV-2 cytotoxicity and may involve inhibition of peroxisome proliferator activated receptor alpha (PPARα). Fenofibrate, a PPAR-α activator, modulates cellular lipid metabolism. Fenofibric acid has also been shown to affect the dimerization of angiotensin-converting enzyme 2, the cellular receptor for SARS-CoV-2. Fenofibrate and fenofibric acid have been shown to inhibit SARS-CoV-2 replication in cell culture systems in vitro…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the pre-hairpin intermediate of the spike protein</strong> - Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors which…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antiviral effect of cetylpyridinium chloride in mouthwash on SARS-CoV-2</strong> - Cetylpyridinium chloride (CPC), a quaternary ammonium compound, which is present in mouthwash, is effective against bacteria, fungi, and enveloped viruses. This study was conducted to explore the antiviral effect of CPC on SARS-CoV-2. There are few reports on the effect of CPC against wild-type SARS-CoV-2 at low concentrations such as 0.001%-0.005% (10-50 µg/mL). Interestingly, we found that low concentrations of CPC suppressed the infectivity of human isolated SARS-CoV-2 strains (Wuhan, Alpha,…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Holistic care of patients with diabetic foot ulcers during the COVID-19 era: integration of Henderson’s Need Theory</strong> - The COVID-19 pandemic has inhibited the practice of diabetic foot ulcer care, particularly in the community. Comprehensive theory-based nursing care is needed to prevent further complications. Unfortunately, a study combining theory with nursing care in diabetic foot ulcer care has not been explored. When caring for patients with diabetic foot ulcers, who are also at increased risk of severe complications from COVID-19, it is important to take a holistic view of the patient and consider all of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of a promising inhibitor from <em>Illicium verum</em> (star anise) against the main protease of SARS-CoV-2: insights from the computational study</strong> - SARS-CoV-2, the causing agent of coronavirus disease (COVID-19), first broke out in Wuhan and rapidly spread worldwide, resulting in a global health emergency. The lack of specific drugs against the coronavirus has made its spread challenging to control. The main protease (M^(pro)) is a key enzyme of SARS-CoV-2 used as a key target in drug discovery against the coronavirus. Medicines derived from plant phytoconstituents have been widely exploited to treat various diseases. The present study has…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>UBR5 Acts as an Antiviral Host Factor against MERS-CoV via Promoting Ubiquitination and Degradation of ORF4b</strong> - Within the past 2 decades, three highly pathogenic human coronaviruses have emerged, namely, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The health threats and economic burden posed by these tremendously severe coronaviruses have paved the way for research on their etiology, pathogenesis, and treatment. Compared to SARS-CoV and SARS-CoV-2, MERS-CoV genome…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antimicrobial peptides: Defending the mucosal epithelial barrier</strong> - The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SEMgsa: topology-based pathway enrichment analysis with structural equation models</strong> - CONCLUSIONS: SEMgsa is a novel yet powerful method for identifying enrichment with regard to gene expression data. It takes into account topological information and exploits pathway perturbation statistics to reveal biological information. SEMgsa is implemented in the R package SEMgraph, easily available at https://CRAN.R-project.org/package=SEMgraph .</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The spike of SARS-CoV-2 promotes metabolic rewiring in hepatocytes</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a multi-organ damage that includes hepatic dysfunction, which has been observed in over 50% of COVID-19 patients. Liver injury in COVID-19 could be attributed to the cytopathic effects, exacerbated immune responses or treatment-associated drug toxicity. Herein we demonstrate that hepatocytes are susceptible to infection in different models: primary hepatocytes derived from humanized angiotensin-converting enzyme-2 mice (hACE2)…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ultrabright nanoparticle-labeled lateral flow immunoassay for detection of anti-SARS-CoV-2 neutralizing antibodies in human serum</strong> - The level of anti-SARS-CoV-2 neutralizing antibodies (NAb) is an indispensable reference for evaluating the acquired protective immunity against SARS-CoV-2. Here, we established an ultrabright nanoparticles-based lateral flow immunoassay (LFIA) for one-step rapid semi-quantitative detection of anti-SARS-CoV-2 NAb in vaccinee’s serum. Once embedded in polystyrene (PS) nanoparticles, the aggregation-induced emission (AIE) luminogen, AIE(490), exhibited ultrabright fluorescence due to the rigidity…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lymphatic coagulation and neutrophil extracellular traps in lung-draining lymph nodes of COVID-19 decedents</strong> - Clinical manifestations of severe COVID-19 include coagulopathies that are exacerbated by the formation of neutrophil extracellular traps (NETs). Here, we report that pulmonary lymphatic vessels, which traffic neutrophils and other immune cells to the lung-draining lymph node (LDLN), can also be blocked by fibrin clots in severe COVID-19. Immunostained tissue sections from COVID-19 decedents revealed widespread lymphatic clotting not only in the lung, but notably in the LDLN, where the extent of…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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<h1 data-aos="fade-down" id="daily-dose">Daily-Dose</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-new-yorker">From New Yorker</a></li>
<li><a href="#from-vox">From Vox</a></li>
<li><a href="#from-the-hindu-sports">From The Hindu: Sports</a></li>
<li><a href="#from-the-hindu-national-news">From The Hindu: National News</a></li>
<li><a href="#from-bbc-europe">From BBC: Europe</a></li>
<li><a href="#from-ars-technica">From Ars Technica</a></li>
<li><a href="#from-jokes-subreddit">From Jokes Subreddit</a></li>
</ul>
<h1 data-aos="fade-right" id="from-new-yorker">From New Yorker</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Is There a Serious Case for a Not-Awful Election for Democrats This Fall?</strong> - One strategist’s “Trumptimism” is another’s “hopium.” - <a href="https://www.newyorker.com/news/letter-from-bidens-washington/is-there-a-serious-case-for-a-not-awful-election-for-democrats-this-fall">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Sins of the High Court’s Supreme Catholics</strong> - The overturn of Roe v. Wade is part of ultra-conservatives’ long history of rejecting Galileo, Darwin, and Americanism. - <a href="https://www.newyorker.com/news/daily-comment/the-sins-of-the-high-courts-supreme-catholics">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Should Former Presidents Get Special Legal Treatment?</strong> - An expert on national-security law offers a framework for how prosecutors can approach politically sensitive cases. - <a href="https://www.newyorker.com/news/q-and-a/should-former-presidents-get-special-legal-treatment">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A TV Face of the Trump Resistance Exits</strong> - Brian Stelter, the host of the CNN show “Reliable Sources,” which was cancelled this week, went from media chronicler to media-chronicled. - <a href="https://www.newyorker.com/news/annals-of-communications/a-tv-face-of-the-trump-resistance-exits">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neil Gaiman on “The Sandman” and the Power of Dreaming</strong> - An adaptation of Gaiman’s series is now a major hit on Netflix, topping charts across the globe. Plus, why so many Black candidates are running in the Republican Party. - <a href="https://www.newyorker.com/podcast/the-new-yorker-radio-hour/neil-gaiman-on-the-sandman-and-the-power-of-dreaming">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-vox">From Vox</h1>
<ul>
<li><strong>The Colorado River drought is coming for your winter veggies</strong> -
<figure>
<img alt="" src="https://cdn.vox-cdn.com/thumbor/nR_7vi-UiLgmxhbxQ7wpr2Up9oc=/481x0:3600x2339/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71264507/AP21222719170483a.0.jpg"/>
<figcaption>
Farmer Will Thelander stands next to a dry canal on his land in Pinal County, Arizona, in July 2021. Some farmers in the county have been forced to fallow their crops due to water cuts on the Colorado River. | Darryl Webb/AP
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
The river waters a lot of our food. What happens as it dries up?
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x9GXsj">
It’s a classic Italian-American meal: a crispy Caesar salad with a plate of marinara pasta.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Jep8qb">
You can find it in restaurants across the country, but depending on the time of year, many of the ingredients come from just one region. Yuma, Arizona, along with California’s Imperial Valley, produces <a href="https://extension.arizona.edu/sites/extension.arizona.edu/files/pubs/az1615.pdf">more than 90 percent</a> of the country’s winter leafy greens and much of its vegetables. Arizona is also a major grower of wheat, which the state exports to Italy for making pasta.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="qmICRg">
Historically, this made a lot of sense. The region has nutritious soil and a warm climate for growing food year-round, even when the rest of the country is frozen over.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EHmeSL">
There’s just one problem: The water that farmers use to grow these crops comes from the Colorado River, and the Colorado River is drying up.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YC8nvC">
The iconic river is in its 23rd year of drought, <a href="https://www.usbr.gov/newsroom/#/news-release/4294">according to</a> the Bureau of Reclamation, and the two largest reservoirs, Lake Powell and Lake Mead, have sunk to historic lows, prompting <a href="https://www.vox.com/science-and-health/23308281/colorado-river-western-drought-satellite-hoover-dam-mead-powell">a series of water restrictions</a>. Under climate change, the drought could <a href="https://www.nature.org/en-us/about-us/where-we-work/united-states/colorado/stories-in-colorado/colorado-charting-a-future-for-colorado-river/#:~:text=The%20Southwest%20is%20seeing%20a,today%2C%20in%20our%20own%20backyards.">worsen</a> in the years ahead.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="h8Ezzf">
That means residents in the West might have less water for lawns and long showers, but it’s a much bigger problem for agriculture because farmers use about three-quarters of all the water that people take from the river. Some farmers have already had to restrict their water supply, and there are much steeper cuts to come.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dU6zSd">
Which brings us to this slightly depressing point: When farmers use less water, they tend to produce less food. And that could cause food prices to go up, even more than <a href="https://fortune.com/2022/07/23/how-much-grocery-prices-have-gone-up-with-inflation/#:~:text=Datasembly's%20Grocery%20Price%20Index%20found,found%20prices%20nationwide%20rose%205.5%25.">they already have</a>. Winter veggies, like lettuce and broccoli, could take a big hit, as could Arizona’s delectable wheat. More concerning still is that the shrinking Colorado River is just one of many climate-related disasters that are threatening the supply and affordability of food.
</p>
<h3 id="0dYY8Y">
Historic water cuts are already hitting farmers
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="iwcDOj">
Meandering 1,450 miles from northern Colorado to the Gulf of California, the Colorado River is the lifeblood of the American West. It provides water to nearly <a href="https://sgp.fas.org/crs/misc/R45546.pdf">40 million</a> people across seven states, Mexico, and more than two dozen tribes, and it irrigates <a href="https://sgp.fas.org/crs/misc/R45546.pdf">millions of acres</a> of land.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yLR0Wz">
The river is governed by a complex set of policies — collectively known as the Law of the River — that dictate how much water each state or tribe receives, and which will lose water first when the government imposes restrictions. (Typically, groups that have been using the water for longer have higher-priority water rights, including Indigenous tribes.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NwEuLN">
Last August, the federal government <a href="https://www.nytimes.com/2021/08/16/climate/colorado-river-water-cuts.html">declared a water shortage</a> on the river for the first time, in response to projections that Lake Mead, the nation’s largest reservoir, would be at just 34 percent of its capacity by the end of 2020. The declaration, known as a Tier 1 shortage, triggered cuts that affected Central Arizona, which has low-priority rights.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="QhpX6v">
Farmers in Pinal County, Arizona, who grow alfalfa, wheat, and other crops, suffered the most, said Paul Brierley, a former farmer who now leads the Yuma Center of Excellence for Desert Agriculture at the University of Arizona. “They’ve had to fallow [stop planting] about 40 percent of their acreage because they lost all their Colorado River water,” he said.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/vYeOVpELiBTmorNb-Idx0L8jQaQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955418/image2.jpg"/> <cite>David McNew/Getty Images</cite>
<figcaption>
Fallowed farmland north of Kingman, Arizona, in June 2021.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WvO5xR">
A withering alfalfa crop could rattle the local dairy industry, Brierley said. Dairy farmers use the flowering plant to feed cows, and when water restrictions take effect, alfalfa is one of the first crops they stop planting.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gg2sfK">
The Tier 1 shortage, alone, may cause prices of milk, yogurt, and other products to spike, at least in Arizona. But as of this summer, the river is already beyond a Tier 1 shortage, and states are facing additional cuts. The impacts could be much farther reaching.
</p>
<h3 id="t9ROTR">
Less water could mean more expensive food
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="MCWO7F">
This summer, the water level in Lake Mead reached a record low of just <a href="https://www.usbr.gov/lc/region/g4000/hourly/hourly.html">1,042 feet</a> above sea level (it was around <a href="https://www.usbr.gov/lc/region/g4000/hourly/mead-elv.html">1,200 feet</a> above sea level in 2000). The reservoir is now <a href="https://earthobservatory.nasa.gov/images/150111/lake-mead-keeps-dropping#:~:text=Continuing%20a%2022%2Dyear%20downward,just%2027%20percent%20of%20capacity.">just over a quarter</a> full. If it drops much lower, the reservoir could hit “dead pool” status, meaning that water can’t travel downstream through the Hoover Dam, let alone <a href="https://www.vox.com/23292669/drought-2022-power-energy-grid-lake-mead-climate-heat-hoover-dam">generate electricity</a>.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AJvBT2">
“Without action, we cannot protect the system and the millions of Americans who rely on this critical resource,” Bureau of Reclamation commissioner Camille Calimlim Touton said on a call with reporters earlier this week.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="olMoBl">
On the call, Touton declared the first-ever Tier 2 shortage, which triggers additional cuts that impact Arizona, Nevada, and Mexico.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WNfVQx">
Her announcement followed a Senate hearing in June, in which she advised officials in the seven states that use water from the Colorado River to come up with a plan to cut an additional<em> </em>2 million to 4 million acre-feet from their supply, on top of the Tier 2 cuts. (An acre-foot is the amount of water needed to fill an acre with one foot of water.)
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4jsn7U">
That does not bode well for farmers and those of us who buy their products. While previous cuts have caused some disruptions in Central Arizona, the impact of a 2-4 million acre-foot reduction — or up to <a href="https://www.cnn.com/2022/08/16/us/colorado-river-water-cuts-lake-mead-negotiations-climate/index.html">25 percent</a> of what the basin states currently use — will be more widespread. Withholding that water will likely affect farms in Yuma, the Imperial Valley of Southern California, and other epicenters of food production.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kaXl6I">
“The [food] system can adapt, but 2-4 million is really a game changer,” said George Frisvold, an agriculture economist at the University of Arizona. “If it gets to the point where people actually have to start cutting back on veggie production, then you’re going to see price increases.”
</p>
<div>
<div class="c-image-grid">
<div class="c-image-grid__item">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/r8szTIr4wX260_iz8IES5Ja_ozM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23957760/GettyImages_1318767556.jpeg"/> <cite>Jon G. Fuller/VWPics/Universal Images Group via Getty Images</cite>
<figcaption>
Rows of red and green leaf lettuce grow on a farm near Yuma, Arizona, in January 2021.
</figcaption>
</figure>
</div>
<div class="c-image-grid__item">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/a8A8bkQXihpWGdWF8Dw1nLspY_M=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955397/GettyImages_1318761012.jpg"/> <cite>Jon G. Fuller/VWPics/Universal Images Group via Getty Images</cite>
<figcaption>
An irrigation canal brings water from the Colorado River to farms in the desert near Yuma, Arizona, in January 2021.
</figcaption>
</figure>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="dYdUDD">
The first crops to get hit — other than alfalfa and other animal fodder — will likely be produce that farmers plant annually (or more often) like lettuce, broccoli, and tomatoes. These are short-term investments and farmers can decide whether or not to plant them on a yearly basis.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="kdmpI5">
In contrast, many fruits, nuts, and other tree crops are longer-term bets that can take years to pay off and tend to be more valuable. Farmers are not going to let, say, almond trees wilt if they can avoid it.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Nfz62S">
“When water supplies aren’t available, farmers have to make decisions on what they can and can’t plant,” said Mike Wade, executive director of the nonprofit California Farm Water Coalition.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tDT0Ow">
Consider a farmer that grows processing tomatoes in California for foods like ketchup or marinara, Wade said. If there isn’t enough water for the growing season, the farmer might not even put the plants in the ground. “Then the supply is reduced to the cannery, which has the effect of increasing prices down the line,” Wade said. “That makes the products that consumers buy in the store more expensive.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3dcirr">
Water cuts could also hurt wheat production in Arizona, said Jeffrey Silvertooth, a plant and soil scientist at the University of Arizona. The region is a major supplier of durum wheat to Italian pasta companies, he said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="o3t1Db">
If a farmer has 20 percent less water, they may choose to leave the ground fallow in the winter instead of planting wheat, Brierley said. “That’s a rational decision that would impact the supply of wheat. And it’s <a href="https://www.vox.com/23171151/ukraine-grain-wheat-russia-black-sea-odesa-food-crisis">not a good time to produce less wheat</a>,” he added, nodding at the war in Ukraine, <a href="https://www.fas.usda.gov/sites/default/files/2022-05/Ukraine-Factsheet.pdf">one of the world’s largest wheat producers</a>, which has already constricted supply of the grain.
</p>
<h3 id="5U3fQO">
Should you be worried?
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="snGLQ0">
The good news is that, on its own, the drought-related supply squeeze isn’t likely to translate to enormous price increases, Frisvold said. A head of lettuce isn’t going to double in price overnight. A box of dried pasta probably won’t bankrupt you.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AgzA8V">
Only a portion of the retail price of food is tied to the cost of actually growing it, and thus, to supply; the rest is related to things like marketing and transportation.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6wwxFE">
Plus, although plenty of food does depend on the Colorado River, there are farms elsewhere, such as in Iowa, that can help meet demand. When the price of certain crops goes up, farmers in other regions start planting them, said Frank Ward, an agriculture economist at New Mexico State University.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="muOLuq">
So, in a sense, our food system is resilient.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3hpOaU">
What’s concerning, however, is that drought along the Colorado River isn’t the only disaster that’s straining our food supply. Earlier this summer, an extreme heat wave in the Midwest caused <a href="https://www.businessinsider.com/photos-of-drought-devastating-american-farmland-2012-7">corn to wilt</a> and <a href="https://www.npr.org/2022/06/16/1105482394/cattle-kansas-heat-wave">cattle to die</a>. Meanwhile, another heat wave in India <a href="https://www.cbsnews.com/news/india-heat-wave-wheat-prices-soar-climate-change-ukraine-war-supplies/">strangled the supply of wheat</a>. That’s on top of supply chain issues linked to the Covid-19 pandemic.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="5JJOY8">
“It’s kind of like death by a thousand cuts,” Frisvold said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="wEzKVF">
Together, these threats — many of which are worsened by climate change, and accelerating — can destabilize the global supply of food and send prices soaring. They’re part of the reason why you’re paying <a href="https://www.bls.gov/news.release/cpi.nr0.htm">13 percent more</a> for groceries this summer, compared to last year.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/Ij-T3DFlBL6QaBLKbop9P3mDcac=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955402/GettyImages_566013103.jpg"/> <cite>Irfan Khan/Los Angeles Times via Getty Images</cite>
<figcaption>
Workers inspect an irrigation system on a broccoli farm in Imperial Valley, California, in October 2011.
</figcaption>
</figure>
<h3 id="dnCxVG">
Toward a more stable (and affordable) supply of food
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="L8AQIe">
If water is running out, one solution is to simply use less of it. Farmers can switch to crops that aren’t as thirsty — from pecans to grapes, for example — or use technologies to water their crops more precisely.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PWNPih">
More environmentally friendly styles of agriculture can also help farms survive extreme drought. Planting cover crops, for example, helps lock moisture in the soil, and switching to an agroforestry-style farm, where trees are integrated into the landscape, can provide valuable shade.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CwIkTU">
These changes come at a cost, but the federal government is willing to help pay for at least some of them. The Inflation Reduction Act, which President Joe Biden signed into law earlier this week, includes <a href="https://www.vox.com/science-and-health/2022/8/15/23301352/inflation-reduction-act-farms-climate-wildlife">nearly $20 billion for farmland conservation</a> and $4 billion for drought relief in the West. The federal spending on drought may help compensate farmers for water cuts and help them develop more efficient farms, Brierley said.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tCakF8">
But ultimately, the US will have to do much more to ensure a stable and affordable supply of food. Drought is a problem, yes, but it’s linked to the much bigger issue of climate change. Without swiftly curtailing carbon emissions, responding to the shrinking Colorado River is just a temporary fix.
</p></li>
<li><strong>House of the Dragon and the Targaryen family, explained</strong> -
<figure>
<img alt="Rhaenys (Eve Best), “the Queen that Never Was,” in HBO’s&amp;nbsp;House of the Dragon." src="https://cdn.vox-cdn.com/thumbor/IdU1YFyQhoA8jskL4e8F6KqB1jY=/49x0:1457x1056/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/71261002/eve_best.8.jpeg"/>
<figcaption>
Rhaenys (Eve Best), “the Queen that Never Was,” looks at her husband Corlys (Steve Toussaint) in HBO’s <em>House of the Dragon</em>. | Ollie Upton/HBO
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
HBO’s Game of Thrones prequel reveals a period of turbulence and upheaval for Daenerys’s formidable family.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ilgXug">
<em>House of the Dragon</em>, the long-awaited prequel to <em>Game of Thrones</em>, is finally here, and you know what that means: It’s time for a refresher course on the Targaryens — the family that ruled for three centuries over all of Westeros. Thanks to one talented fanartist, we have <a href="https://www.vox.com/culture/2017/7/17/15982450/house-targaryen-family-tree-fanart">a gorgeous family tree</a> to help you figure out what’s happening when the show premieres Sunday night.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="u9FTt8">
The series adapts portions of George R.R. Martin’s <em>Fire and Blood</em>, a collection of stories accompanying the <em>Song of Ice and Fire</em> series upon which the <em>Game of Thrones</em> universe is based. The book is a partial history of the Targaryens, with whom fans will be well-acquainted, since their reign stretches from Daenerys all the way back to the first king of Westeros. They’re famed for their ability to tame dragons; hence, “house of the dragon.” That rare talent helped the Targaryens establish an immense dynasty over the realm; but as always when we’re dealing with <em>Game of Thrones</em>, even empires can topple, and the iron throne is never a safe place to sit.
</p>
<div class="c-float-right">
<div id="rlXeGj">
<div>
</div>
</div>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="x2mYVN">
Because we’re dealing with a prequel, we’re going to be dropping some major plot points for both the book series and the forthcoming show, so be warned: from here on in, there be dragons and spoilers!
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BVPPpG">
If you’re expecting familiar faces, you’re in for a shock: <em>House of the Dragon</em> takes place 190 years or so before the storyline of <em>Game of Thrones</em> begins, and though many things have stayed the same through the centuries — King’s Landing is still the capital of Westeros, the Starks are still the lords of Winterfell — we have a whole cast of characters to familiarize ourselves with and complicated family dynamics to parse.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="U46c1m">
We’re introduced to some of the key players in <em>House of the Dragon</em>’s first episode, but there’s a major learning curve thanks to the sheer size of the Targaryen family and their tendency to repeat names from generation to generation. Other family trees in this universe are often easier to follow because they’re, for example, <a href="https://awoiaf.westeros.org/index.php/Elmo_Tully#Behind_the_Scenes">all named after the Muppets</a>; but with the Targaryens, you have something like a dozen Aegons, a half-dozen Aemons, a slew of Viseryses, and on and on. Oh, and let’s not forget their infamous tendency to marry each other — a fun Targaryen trait we’ll soon witness.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="ncHMlh">
We won’t know everything the TV series will retain from the books, of course, so a lot of what we’ll be discussing is speculation based on the main plot lines of <em>Fire and Blood</em>. The series has made some changes, but most of the major events in this tumultuous Targaryen era are so far the same.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="98UVKn">
The series plops us in the middle of an ongoing simmering family conflict about — what else? — succession. If you’re confused about where exactly we are in the Targaryen family timeline, never fear: DeviantArt user Maryon B.’s <a href="http://poly-m.deviantart.com/art/House-Targaryen-complete-Family-Tree-614284707">Targaryen family tree</a> is a gorgeous (and <a href="https://poly-hebdo.tumblr.com/post/164019286066/i-did-it-you-guys-they-were-rushing-us-but#notes">GRRM-approved</a>!) road map through three centuries of huge Targaryen broods, internal squabbles, civil war, and, yes, inbreeding.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="PTRFZ0">
We first introduced Vox readers to Maryon’s fanart all the way back in 2016, when she <a href="https://www.vox.com/culture/2017/7/17/15982450/house-targaryen-family-tree-fanart">gave us her insights</a> on the long process of creating the tree. A year later, the tree came in handy to help explain <a href="https://www.vox.com/culture/2017/8/30/16213394/r-l-j-game-of-thrones-fandom-oral-history">one of the series’ biggest plot twists</a>. Now, the “Targtree” can fulfill its ultimate purpose and help us all prep for the upcoming series! <a href="https://cdn2.vox-cdn.com/uploads/chorus_asset/file/6642301/house_targaryen_complete_family_tree_by_poly_m-da5q943.jpg">Click here for the full-size version</a>.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/9CoKBTACYHPaKq81TWF7xql38QE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955175/targ_complete.jpg"/> <cite><a class="ql-link" href="https://www.deviantart.com/poly-m/art/House-Targaryen-complete-Family-Tree-614284707" target="_blank">Poly-M</a>/DeviantArt</cite>
<figcaption>
We stan a lovingly detailed infogram.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="CxelmC">
<em>House of the Dragon</em> lands in the middle of the family tree, about halfway between the time the first Aegon Targaryen, known as Aegon the Conqueror, united all of Westeros, and the final fall of Daenerys Targaryen in the series finale of <em>Game of Thrones</em>. The events depicted in <em>House of the Dragon</em>’s first episode set us up to enter the period highlighted on the family tree as the Dance of Dragons — a time when the question of succession split the Targaryens apart and led to a brutal civil war.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/jaG6E37MCnHa_e7p50I8IfTJerc=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955179/targ_full2.jpg"/> <cite><a class="ql-link" href="https://poly-hebdo.tumblr.com/post/145669673401/i-dont-even-like-house-targaryen" target="_blank">poly-hebdo</a>/Tumblr</cite>
<figcaption>
The Dance of the Dragons era of the Targ family tree.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="WxZqLl">
The years preceding the beginning of the show witnessed a long period of fighting known as the Faith Militant Uprising that ended only when the reigning king, the cruel Maegor I, died mysteriously. After his death, the only remaining son of the previous king, Jaehaerys I, succeeded to the throne.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="21KRBy">
But because of the preceding generation of chaos, the line of succession isn’t clear. So, at the start of <em>House of Dragons</em>, Jaehaerys summons a council to choose the next heir. The two Targaryens with the best claim to the throne are his grandson, Viserys, and his granddaughter-slash-grandniece, Rhaenys. They’re both his grandchildren, so both have an equal claim to the throne. But because Westeros has never had a queen as ruler before, the council chooses Viserys to be the next ruler; thus he becomes Viserys I.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="KMz4RQ">
Still, Rhaenys, nicknamed “the Queen that Never Was,” is a popular member of the royal family, and many people still profess loyalty to her and her progeny. Meanwhile, until Viserys can produce a male heir — or until the court decides it’s fine for a woman to rule — his brother Daemon is next in line to succeed to the throne. But Daemon isn’t exactly a popular choice.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="yHrGRK">
Let’s take a closer look at our main players. If the books are any indication, their projected storylines won’t be all roses.
</p>
<h3 id="PKGuDk">
Rhaenys (Eve Best) and Corlys (Steve Toussaint)
</h3>
<div class="c-float-right">
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/QgfKUz_xaHk_Pg9vWYqVt5jlI04=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955183/targ_rhaenys.jpg"/> <cite><a class="ql-link" href="https://poly-hebdo.tumblr.com/post/138880707336/rhaenys-the-queen-who-never-was-targaryen-and" target="_blank">poly-hebdo</a>/Tumblr</cite>
<figcaption>
Rhaenys and her clique.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0sbuLE">
Rhaenys, a.k.a. “the Queen that Never Was,” was the product of a marriage between Jaehaerys’s eldest son Aemon and Aemon’s own aunt, Jocelyn Baratheon. In her adolescence, she gained fame as one of the Targaryen dragonriders as well as for her beauty. At 16, Rhaenys married a man nearly 20 years her senior: the gallant Corlys Velaryon, known as the “Sea Snake” for his daring sea expeditions. (Their age difference seems to be reduced in the TV series.) Together, they make a power couple at court, and their children continue to have a claim to the throne. But because Rhaenys is a woman, and because her oldest heir, Laena, is also a woman, her family continues to be passed over for the line of succession — which frequently puts her and Corlys at odds with King Viserys.
</p>
<h3 id="4FkgOB">
Viserys I (Paddy Considine)
</h3>
<div>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/eK8asd1GZz09ILdGVHt2uG22RLY=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955192/targ_paddy_considine.jpg"/> <cite>Ollie Upton/HBO</cite>
<figcaption>
A wise but foolish king.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="okfUh7">
Viserys, played in the show by Paddy Considine, is a kind and generous king who brings stability to the realm. However, when it comes to the question of succession, he’s fanciful to a fault in his pursuit of a male heir. This leads to him making a horrible decision that results in the death of his first wife, Aemma, and their newborn son. It also leads to him hedging his bets about who his heir should be after he remarries and has more children. His indecision leads the heirs in question — his daughter Rhaenyra and his son Aegon — to battle for the crown.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4RpWId">
This conflict plays out while the king is still alive, leading him into frequent tussles with his own family members as he attempts to wrangle them all into submission and clear the way for his daughter, Rhaenyra, to inherit the throne. However, not infrequently, the one he winds up butting heads with is Rhaenyra herself.
</p>
<h3 id="DjdJTj">
Rhaenyra (Emma D’Arcy)
</h3>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/2L-m522W8fEjMIwcqkYj-bnU1wo=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955196/targ_emma_d_arcy_as_princess_rhaenyra_targaryen.jpg"/> <cite>Ollie Upton/HBO</cite>
<figcaption>
Is she a hero or an antihero? Time will tell.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0EnoCi">
Rhaenyra is Viserys’s firstborn child, the daughter of his first wife Aemma. Clever and athletic, Rhaenyra (played by Milly Alcock as a teen) is at first more interested in riding her dragon, Syrax, than in winning games of thrones. That changes when her father can’t make up his mind who to appoint as his heir, and she becomes first an unwitting pawn and then an active player in the battle for succession.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="4mY0wr">
Following Aemma’s death, Viserys marries Alicent Hightower (played by Emily Carey as a younger woman), a girl only a few years older than Rhaenyra herself. As she grows up, Rhaenyra finds herself at odds with her former friend Alicent, and soon they’re locked in a battle over whether Rhaenyra or Alicent’s son Aegon should take the throne after Viserys’s death.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AsbvQc">
Their supporters become divided into “blacks” and “greens” after the two women make fashion statements at a tourney following the marriage; “blacks” are Rhaenyra’s supporters after she dons a gown in traditional Targaryen red and black. The greens and the blacks aren’t just about who’s more popular; the greens also represent the widespread belief that a woman shouldn’t be able to inherit the crown. Support for Rhaenyra, a.k.a. identifying as one of the blacks, is a sign of support for women’s equality.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Gs5ncP">
Rhaenyra’s love life is its own dramatic saga. She remains enamored all her life with her own uncle, Daemon, who’s 16 years older. She also has a thing for a dashing knight named Criston Cole (played by Fabien Frankel), who we see getting flirty with her in the first ep. Criston, however, ultimately becomes her enemy after he allies with Aegon and convinces him to go for the crown.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EjFbAd">
Later, Viserys, trying to dodge his wife Alicent’s suggestion to marry Rhaenyra to their son Aegon, pressures her into marrying Rhaenys’s son Laenor Velaryon instead. Rhaenyra hates this idea — for one thing, Laenor is gay — but Viserys threatens to disinherit her unless she agrees. The two wind up having three strapping sons, but their real father is generally thought to be Rhaenyra’s lover, Harwin Strong (to be played by Ryan Corr), who serves as Rhaenyra’s loyal servant and sworn shield. Or, as <a href="https://poly-hebdo.tumblr.com/post/142905095696/dont-call-them-strongs-even-if-they-are-in-both">our artist Maryon said</a>, “Don’t call them Strongs — even if they are in both ways.”
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/oQLF4nhNevYR7Bzl9inJtewgdMY=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955199/targ_strong.jpg"/> <cite><a class="ql-link" href="https://poly-hebdo.tumblr.com/post/142905095696/dont-call-them-strongs-even-if-they-are-in-both" target="_blank">poly-hebdo</a>/Tumblr</cite>
<figcaption>
Rhaenyra’s real nuclear family?
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="EXeUSZ">
Things don’t end well for Rhaenyra and Harwin, unfortunately — the situation is just too unstable for Rhaenyra to keep a lover on the side while the line of succession is in dispute, and the king sends Harwin into exile. Rhaenyra responds by secretly marrying her uncle Daemon after Laenor Valeryon’s death — which infuriates her father.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="O2C8pW">
In the ensuing drama, and with conflict heating up between Rhaenyra and Alicent and Aegon, she relocates to the Targaryen keep of Dragonstone, which means she’s not around when King Viserys dies. Instead of telling Rhaenyra about her father’s death, Alicent and Aegon prepare to anoint Aegon as the new king. When Rhaenyra finds out, she enters into a rage from which she never fully recovers. In her quest to take the throne for herself, she winds up going to some very dark places. But the two sons she bears with Daemon, Viserys II and Aegon III, ultimately do both become rulers of Westeros, so perhaps in the end, she wins.
</p>
<h3 id="Cco8Jz">
Daemon (Matt Smith)
</h3>
<div>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/y8BkASL38gtz3S-zEJMleB0zNsg=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955203/targ_matt_smith.jpg"/> <cite>Ollie Upton/HBO</cite>
<figcaption>
He’s hot, then he’s cold.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6L41tN">
Daemon Targaryen is popular with everyone except the people who can make him the next king. King Viserys’s right-hand man, Otto Hightower (played by Rhys Ifans), repeatedly blocks Daemon from becoming the next heir and then chooses Rhaenyra over him as successor — at least, he does until his own daughter Alicent marries the king.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mL1agk">
But for all his enemies suspect him of plotting to take over the throne, Daemon, a.k.a. the “rogue prince,” has better things to do, like seducing his brother’s daughter Rhaenyra and conquering his own kingdom. Daemon is congenial but aggressive, and he has a bad habit of killing all his potential love rivals. He falls for Rhaenys’s daughter Laena Velaryon — a convenient match in terms of maintaining his place at court — but Laena’s already engaged. No problem; he kills his rival in a duel.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oar5as">
Later, rumor has it he murders his own brother-in-law, Laenor Velaryon, then married to Rhaenyra. Then he maybe seals the deal by murdering Rhaenyra’s lover Harwin, thereby successfully taking out both of his rivals for Rhaenyra’s hand, and marrying her. Ultimately, all of this may have just been Daemon’s way of getting as close to the throne as he could. In short, Daemon Targaryen is not a man you want to cross.
</p>
<h3 id="k3xk0B">
Mysaria (Sonoya Mizuno)
</h3>
<div>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/PcxSrlIvyvTWfSI2iXzfyujc8Lc=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955218/targ_sonoya_as_mysaria.jpg"/> <cite>Ollie Upton/HBO</cite>
<figcaption>
A dancer with eyes everywhere.
</figcaption>
</figure>
</div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="nt7Xjk">
Sometimes called “Misery,” Mysaria starts out as a sex worker in King’s Landing, but quickly becomes indispensable to her patron and lover Daemon as a source of information. From there, she becomes the ranking spy first for Daemon and later for Rhaenyra, which makes her one of the most powerful people in Westeros. Not too shabby for a dancer from Essos.
</p>
<h3 id="uYwfFT">
Alicent Hightower (Olivia Cooke)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="RjZKDh">
On one level, the Dance of Dragons is really about the clash between two former friends, Alicent and Rhaenyra, who grew up in the king’s court together only to be pulled into opposite sides of the ongoing dispute over who will inherit the throne. The Hightowers were and are a small but powerful house; Alicent’s father, Otto Hightower, served as Hand of the King to Jaehaerys and now serves as Hand to Viserys.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="P448xf">
The Hightowers haven’t always had the most fruitful relationship with the crown; several generations prior, Maegor I’s unsuccessful marriage to a Hightower provoked dissension among her powerful family and kicked off the events leading to the Faith Militant Uprising. Now, Otto schemes successfully to present his daughter Alicent to Viserys as a suitable bride. They are married when she’s just 18.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/6Z9dchqr7vJ6JRFfyHPA9jog6zE=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955220/targ_milly_alcock_as_young_rhaenyra_emily_carey_as_young_alicent.jpg"/> <cite>Ollie Upton/HBO</cite>
<figcaption>
Rhaenyra and Alicent are the best of friends, until they aren’t.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="djLxpE">
A note on royal marriages here: In Martin’s history of the Targaryens, the timeline is often compressed, with many royals forming alliances and marrying at very young ages. In <em>Fire and Blood</em>, Viserys marries Aemma when he’s just 16 and she’s only 11. (She dies in childbirth at age 23.) He later marries Alicent at age 29, when she’s 18 and his own daughter Rhaenyra is just 9.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="C5HF4F">
In <em>House of the Dragon</em>, all of these characters have been aged up significantly except for Alicent, who is still 18-ish. This makes her much closer in age to Rhaenyra — much more of a peer than a stepmother twice her age. But that also means that instead of an 18-year-old being coerced into marrying a 29-year-old, she’s an 18-year-old being coerced into marrying a man of about 50. This of course makes the issues of consent, control, and power imbalance even starker, and arguably makes Alicent’s role in the story to come one that’s less about power-seeking and more about survival.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="hn8Mpw">
Initially, Alicent wants her own son, Aegon, to marry Rhaenyra, even though there’s a considerable age difference between them. (That they’re also half-siblings is just fine, of course.) When that doesn’t fly with Viserys, she ends up promoting Aegon as heir above Rhaenyra. The women’s conflict deepens when Rhaenyra’s former crush, Criston Cole, becomes loyal to the Hightowers and ultimately becomes Alicent’s personal sworn shield. Alicent’s color is green, which makes her supporters “the greens” opposed to Rhaenyra’s “blacks.”
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/ApmE05XKW_Ly3q-dux_dCiNaexA=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/23955224/targ_alicent.jpg"/> <cite><a class="ql-link" href="https://www.deviantart.com/poly-m/art/House-Targaryen-complete-Family-Tree-614284707" target="_blank">poly-m</a>/DeviantArt</cite>
<figcaption>
Alicent’s fierce and fiercely loyal brood.
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="DajGt6">
Alicent is a tricky figure; she alternately tries to make peace with Rhaenyra and avoid conflict while strategizing ways to put Aegon on the throne. Rumors abound that she poisoned her own husband, the king, in order to hasten his demise and crown Aegon while Rhaenyra’s back was effectively turned.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="cDh07J">
Like most of our other players, the pursuit of the throne doesn’t end well for her or many of her progeny. But she does pull off her original goal; she survives to see her son become ruler of Westeros. Through succeeding generations, the Hightowers continue to remain wealthy and powerful; following the conquest of Dorne, they become loyal to House Tyrell. (If the name is familiar, Margaery Tyrell’s mother is a Hightower.)
</p>
<h3 id="iQye3n">
Aegon II (Tom Glynn-Carney)
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="BVOODO">
It’s easy to see why there was so much resistance to Alicent’s son Aegon becoming king: He’s like a smarmier, hornier Prince Joffrey. You’ll see.
</p></li>
<li><strong>This Targaryen family tree explains Jon Snow’s parentage — and sets up House of the Dragon</strong> -
<figure>
<img alt="Jon Snow in Game of Thrones" src="https://cdn.vox-cdn.com/thumbor/4Jz9Jfgd0osfEIHsRv4Jl2fazgw=/107x0:1814x1280/1310x983/cdn.vox-cdn.com/uploads/chorus_image/image/55747343/804helensloan_hbo_3__13298.24.jpg"/>
<figcaption>
Who are Jon Snow’s parents? | Courtesy of HBO
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Untangling one of Games of Thrones’ biggest secrets.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xaEiHK">
<em><strong>Editor’s note, August 19, 2022: </strong></em><em>This piece was first published in 2016 and updated following the season seven finale of </em>Game of Thrones<em>. </em><a href="https://www.vox.com/e/23076114"><em>Click here</em></a><em> to read about how the Targaryen family tree relates to HBO’s new prequel series</em> House of the Dragon<em>.</em>
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="xYNKO4">
In <a href="https://www.vox.com/culture/2017/8/28/16212970/game-of-thrones-finale-recap-dragon-wolf-winners-losers"><em>Game of Thrones</em>’ season seven finale</a>, Jon Snow and Daenerys Targaryen finally consummated their slow-burning passion — even though the season six finale’s confirmation of the <a href="https://www.vox.com/2015/5/4/8543525/jon-snow-mother">“R + L = J”</a> equation surrounding Jon’s parentage renders their love an incestuous one between aunt and nephew.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="mu4haT">
The finale also revealed that Jon Snow’s real name is Aegon Targaryen — a twist that might have confused readers of the books <em>Game of Thrones</em> is based on, since that’s also the name of Jon’s long-dead half-brother. We know this half-brother at least <em>existed</em> in the show’s universe, because Oberyn Martell famously fought the Mountain <a href="https://www.vanityfair.com/hollywood/2017/08/game-of-thrones-what-is-jon-snows-real-name-aegon-targaryen-season-7-episode-7-dragon-wolf">partly to avenge his death</a> and the death of his sister. It’s not clear, however, if he was still named Aegon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="NbxmUA">
Confused? That’s understandable. To know why Lyanna Stark might have wanted to name her son Aegon with her dying breath, you might need a refresher course on the immense Targaryen dynasty — the family that ruled for three centuries over all of Westeros. And if you’re having trouble remembering what part the original Aegon, Jon’s namesake, played in this litany of names, you’re in luck: An enterprising fan artist has drawn the entire House Targaryen family tree, and the results are as educational as they are gorgeous.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pIbw8N">
DeviantArtist user Maryon B.’s work is a <a href="http://poly-m.deviantart.com/art/House-Targaryen-complete-Family-Tree-614284707">gorgeous take</a> on the complicated, once-mighty dynasty of the Targaryens that doubles as a handy reminder of just where Jon Snow fits into all of this (click <a href="https://cdn2.vox-cdn.com/uploads/chorus_asset/file/6642301/house_targaryen_complete_family_tree_by_poly_m-da5q943.jpg">here</a> for the full-size version):
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/mnvy-G4NceahW8e1W7kiJJPBBmU=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/6642301/house_targaryen_complete_family_tree_by_poly_m-da5q943.jpg"/>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="2O0McA">
Maryon is a 28-year-old French freelance artist and video game developer currently living in Helsinki. She’s also a die-hard <em>Game of Thrones</em> fan, which might explain why she’s illustrated the entire lineage of House Targaryen (home of one Daenerys, Mother of Dragons) from George R.R. Martin’s <em>A Song of Ice and Fire</em> series of novels — even though, as she says in her description of the project on<strong> </strong><a href="http://poly-m.deviantart.com/art/House-Targaryen-complete-Family-Tree-614284707">DeviantArt</a>, “I DON’T EVEN LIKE HOUSE TARGARYEN WHY DID I DO THIS[?]”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="XWjwpa">
“I actually started the Tree out of spite because all their descriptions (and fan representations) make them look the same — beautiful, silver-haired and purple eyes,” she told Vox via email in 2016, after first drawing the tree, “and it frustrated me to see them as elf-clones.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Or5Akn">
Maryon’s frustration is understandable. The Targaryens are much more than pretty blondes with big pets, and their convoluted dynasty has vast repercussions for the present and future of Westeros.
</p>
<h3 id="xQF6FD">
The name “Aegon” invokes the men who united all of Westeros — until Jon Snow’s father inadvertently helped shatter the realm
</h3>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/N4U5qhv6rDAT4jM2jONlmSzYyhM=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/9129069/Screen_Shot_2017_08_28_at_12.21.43_PM.png"/>
<figcaption>
Not shown in this picture: Rhaegar’s <em>other</em> marriage to Lyanna Stark and the new Aegon (a.k.a. Jon Snow).
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Y3LHKo">
As <em>Game of Thrones</em> fans have heard time and again, the powerful Targaryen family unified the Seven Kingdoms. This is mainly thanks to the <em>first</em> Aegon Targaryen, known as Aegon the Conqueror. Several other Aegons followed — including the wise and kindly Aegon V, better known to book fans as “Egg” from Martin’s <a href="https://en.wikipedia.org/wiki/Tales_of_Dunk_and_Egg"><em>Dunk and Egg</em></a> prequel novellas.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="AEelfl">
But though Egg stabilized the country and ruled over a harsh winter, the end of his reign <a href="http://io9.gizmodo.com/george-r-r-martin-made-me-feel-unspeakably-depressed-y-1756902020">wasn’t exactly a career high point</a>. And unfortunately for Westeros, Aegon V’s grandson was the “Mad King,” Aerys II, better known as Daenerys’s deceased father.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="SI3SYu">
Aerys’s son, Rhaegar Targaryen — Daenerys’s brother, the crown prince and heir to the throne, whom we now also know as Jon Snow’s father — fell in love with Lyanna Stark, Ned Stark’s sister, even though he was already married to Elia Martell. A further complication: Lyanna was already engaged to Robert Baratheon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="rrSauW">
<em>Game of Thrones</em> season seven revealed crucial new context to this backstory: We now know that Rhaegar secretly had his marriage to Elia annulled so he could marry Lyanna Stark sometime before his death and the birth of their son. But Robert believed (or wanted to believe) that Rhaegar had kidnapped and raped Lyanna — and the resulting conflict culminated in a horrific end to the peace between the families, as the Mad King burned Lyanna’s father, Rickard Stark, alive while her brother Brandon watched. This led to an uprising that came to be known as Robert’s Rebellion, in which the Baratheons joined House Stark to fight and ultimately overthrow the Targaryens.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="3qUrwL">
It was during Robert’s Rebellion that Robert defeated Rhaegar in battle. After Rhaegar’s death, Robert’s fearsome henchman Gregor Clegane murdered Rhaegar’s wife — or, as we now know, his former wife — Elia Martell, and Rhaegar’s two young children, Aegon and Rhaenys. The season seven finale revealed that shortly thereafter, Lyanna told Ned Stark that her child, Rhaegar’s last remaining son, was also named Aegon.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="avMe1N">
Will Jon Snow fulfill the reputation of the name of Aegon the Conqueror and Aegon V? Given all the violence and conflict that led to his birth, we can only hope.
</p>
<h3 id="Z2LPcj">
If you think this part of the Targaryen legacy is confusing, wait til you see the entire lineage
</h3>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="oMQ2Bh">
The full Targaryen family tree contains more than 100 characters and spans 16 generations of entirely fictional history.
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="pKgoTf">
Here’s a look at only one character from this broad tapestry: the second Rhaenys Targaryen. Known in the annals of Westeros history as the “queen who never was,” Rhaenys was a dragon rider whose claim to the throne was passed over in favor of her brother. She married Corlys Velaryon and died fighting a battle on dragonback at the age of 52:
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/l3__qblH-vX9MwW1c0TncB6F4zQ=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/8864851/Screen_Shot_2017_07_17_at_11.18.15_AM.png"/> <cite><a href="http://poly-m.deviantart.com/art/The-Queen-Who-Never-Was-589377884">poly-m</a> / DeviantArt</cite>
<figcaption>
Rhaenys Targaryen
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="viLx9n">
Rhaenys’s great-grandmother was Alyssa Velaryon, who joined the Targaryen dynasty by marrying Aenys I, a politically wily man who took the throne amid great upheaval. They had six children before Aenys was killed and Alyssa taken hostage by her husband’s half-brother Maegor. (And from there, things get <em>really</em> complicated.)
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/iQ7nom8z2YFUsEYX92KRSDIk_Vs=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/8864859/aenys_i_family_by_poly_m_d9sge5k.jpg"/> <cite><a href="http://poly-m.deviantart.com/art/Aenys-I-Family-591989672">poly-m</a> / DeviantArt</cite>
<figcaption>
“Dead Targs, dead Targs everywhere.”
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="Qul8jg">
Further down the family tree, there’s House Blackfyre, an illegitimate house sanctioned by the lust-ridden King Aegon Targaryen IV, who’s generally considered the worst king ever. His decision to legitimize all of the bastard children he fathered with his <a href="http://poly-m.deviantart.com/art/Royal-Mistresses-577926819">many mistresses</a> — announced from his deathbed — prompted five generations of battles for the throne known as the Blackfyre Rebellions.
</p>
<figure class="e-image">
<img alt=" " src="https://cdn.vox-cdn.com/thumbor/kjkRpNnmiOj2kw93BSwFZMEy2eo=/800x0/filters:no_upscale()/cdn.vox-cdn.com/uploads/chorus_asset/file/8864875/house_blackfyre_by_poly_m_d9wn3rv.jpg"/> <cite><a href="http://poly-m.deviantart.com/art/House-Blackfyre-599021275">poly-m</a> / DeviantArt</cite>
<figcaption>
House Blackfyre
</figcaption>
</figure>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="YltU0Z">
Maryon says she got into Martin’s <em>Song of Ice and Fire</em> novels and related writing during the long hiatus between seasons two and three of <em>Game of Thrones</em>. She started the Targaryen family tree project more or less on accident after drawing Baelor Breakspear and Maekar, characters who figure prominently in <em>Tales of Dunk and Egg</em>, Martin’s aforementioned collection of related novellas set in the <em>Song of Ice and Fire</em> universe. Naturally, the project spiraled:
</p>
<blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="zZGbBa">
[I]t got me interested in their ancestors, so I worked from there. At first I never thought I’d do the whole bunch, but it’s when I realized that I was already halfway through just by making Maekar’s descendants that I gave in: “While I’m at it, might as well do the rest…”
</p>
</blockquote>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="gu6mfq">
Maryon says the project turned out to be “a very challenging artistic exercise, to keep on coming up with facial variety all while maintaining the same ‘silver hair-purple eyes’ features and some genetic similarities.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="lVaQVx">
“I had to find inspiration and study some real people’s faces so I learned a lot since I started.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="0jwa4H">
Above all, a look at the full family tree reveals how often and how strategically the Targaryens secured the future of their line by marrying into other powerful families like the Martells, the Baratheons, and the Velaryons, just as many figures in real-world history have done. And when Maryon was finished, she says she’d actually become fonder of the Targaryens than she was when she began:
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="tNb9Vl">
“[I]n the end it made me appreciate House Targaryen much more since now I share a personal story with each and every one of them, and I would suggest anyone who likes <em>Game of Thrones</em> to be curious about them because they have a lot of stories to tell.”
</p>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom" id="6iloZX">
You can see these and many more excerpts from the Targaryen family tree, as well as other <em>Game of Thrones</em> portraits, on <a href="http://poly-m.deviantart.com/gallery/44214023/Game-of-Thrones">Maryon’s DeviantArt page</a>. She’s <a href="https://www.reddit.com/r/ImaginaryWesteros/comments/4ncnf9/there_it_is_the_complete_targaryen_family_tree_by/d43ay59">stated</a> that she hopes to eventually produce a print version of the full family tree, but in the meantime she’s done a few more complicated <em>Game of Thrones</em> projects, including <a href="http://poly-m.deviantart.com/art/Game-of-Thrones-Tarot-Part-1-407951065">a set</a> of <a href="http://poly-m.deviantart.com/art/Game-of-Thrones-Tarot-Part-2-418562802">Major Arcana</a> <a href="http://poly-m.deviantart.com/art/Game-of-Thrones-Tarot-Part-3-426660762">tarot cards</a>.
</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-sports">From The Hindu: Sports</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Scramjet obliges in Belmont Prince Plate</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Gokulam Kerala ruled out of AFC Women Club Championships, will return to India</strong> - 23-member team, led by India captain Ashalata Devi, were left stranded in Tashkent for four days since arriving at the Uzbekistan following the FIFA ban on India</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Star Is Born, Multiencrypted and Redifined please</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Artemis Ignacia, Slainte and Pense’e impress</strong> -</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Khalin Joshi beats Arjun to title</strong> - 14-under 274 a new record for the lowest winning card at the course</p></li>
</ul>
<h1 data-aos="fade-right" id="from-the-hindu-national-news">From The Hindu: National News</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Tripura CM voices concern over law and order situation in industrial belt, asks cops to be proactive</strong> - Tripura CM Manik Saha said action has not been initiated against law breakers in several cases, despite the registration of FIRs, and asked the police in West Tripura district to “act as per rules”.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ten-day House session from tomorrow</strong> - To bring in fresh Bills to replace ordinances that have lapsed</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Islands in Odisha’s Hirakud reservoir host ground nesting by birds away</strong> - Vast swathes of water act like shield against predators.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Every pregnant woman deserves dignity during motherhood: Delhi High Court</strong> - The court said giving birth to a child in custody would not only be traumatic for the mother but also impact the child adversely</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Kerala women drive tractors to boost farming and self-confidence</strong> - Driving lessons under Centre’s Mahila Kisan Sashaktikaran Pariyojana programme</p></li>
</ul>
<h1 data-aos="fade-right" id="from-bbc-europe">From BBC: Europe</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine war: Russia to allow inspectors at Zaporizhzhia nuclear plant - Putin</strong> - Russia captured the Zaporizhzhia facility in March and is accused of using it as a military base.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine nuclear plant: How risky is stand-off over Zaporizhzhia?</strong> - International leaders warn of potential disaster at the Russian-occupied Zaporizhzhia plant.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sanna Marin: Finnish PM reveals she has taken drug test</strong> - Sanna Marin was speaking to reporters after videos showed her partying with celebrities.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Freya the walrus: Did she have to be euthanised?</strong> - After becoming a tourist attraction in Oslo, a travelling walrus was killed. Was that right?</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ukraine’s Crimean fightback having ‘psychological impact’ on Russia</strong> - Western officials reveal the impact of recent Ukrainian strikes on the Russian-occupied peninsula.</p></li>
</ul>
<h1 data-aos="fade-right" id="from-ars-technica">From Ars Technica</h1>
<ul>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Behold this award-winning image of fungus making a fly its “zombie” slave</strong> - Plus eight other winning images in 2022 BMC Ecology and Evolution image competition. - <a href="https://arstechnica.com/?p=1874865">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Botometer creator says Musk’s Twitter spam estimate “doesn’t mean anything”</strong> - With Botometer tool, you can “choose any threshold… to get any result you want.” - <a href="https://arstechnica.com/?p=1874991">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ethereum’s “Merge” is about to put every ether miner out of work</strong> - The ambitious change is expected to cut energy consumption by a factor of 1,000. - <a href="https://arstechnica.com/?p=1874521">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lucid gives the Air a sporty makeover, launches new Sapphire sub-brand</strong> - At $249,000, the Lucid Air Sapphire will be a rare thing indeed. - <a href="https://arstechnica.com/?p=1874896">link</a></p></li>
<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Qualcomm is jumping back into the server CPU market with Nuvia acquisition</strong> - Nuvia—a company founded by ex-Apple CPU engineers—will also tackle server designs. - <a href="https://arstechnica.com/?p=1874897">link</a></p></li>
</ul>
<h1 data-aos="fade-right" id="from-jokes-subreddit">From Jokes Subreddit</h1>
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<li><strong>A guy asks his girlfriend for a blowjob.</strong> - <!-- SC_OFF -->
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She says “No, you won’t respect me enough to marry me and I love you.” After they’re married he asks her again, she says “Not yet, you won’t want to have children with a woman who you don’t respect.” So after they have children he asks her again, she says I’m still afraid you’ll lose respect for me, just wait." So years go by, they’re grand parents now and he says “Look, I have proven my love and respect, you are my wife, you are the mother of my children, the grandmother to our grandchildren, I just want this little thing.” So that evening she makes his wish come true and gives him the blowjob he’s waited for so long for. Suddenly the phone rings, he gets up and answers it then covers the mouthpiece and says “Hey Cocksucker, it’s for you.”
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/ramdasani"> /u/ramdasani </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/wt1xsy/a_guy_asks_his_girlfriend_for_a_blowjob/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/wt1xsy/a_guy_asks_his_girlfriend_for_a_blowjob/">[comments]</a></span></p></li>
<li><strong>Who runs Mexican Amazon?</strong> - <!-- SC_OFF -->
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Jeff Pesos
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It’s a silly joke but I thought of it on my own today! I found a 200 peso bill on the ground today and I was saying pesos in different accents out loud with a coworker when the joke popped into my head. I don’t think I’ve heard it anywhere before. After I got home and searched it here I realised it hasn’t been told this way on this subreddit yet either. So I’m claiming it as an original joke.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/JayteeBurke"> /u/JayteeBurke </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/wsqq3a/who_runs_mexican_amazon/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/wsqq3a/who_runs_mexican_amazon/">[comments]</a></span></p></li>
<li><strong>How did the foot fetishist cheat on his girlfriend?</strong> - <!-- SC_OFF -->
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He got off on the wrong foot.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/HeIsSoWeird20"> /u/HeIsSoWeird20 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/wsnbln/how_did_the_foot_fetishist_cheat_on_his_girlfriend/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/wsnbln/how_did_the_foot_fetishist_cheat_on_his_girlfriend/">[comments]</a></span></p></li>
<li><strong>A priest goes to the barber for a haircut.</strong> - <!-- SC_OFF -->
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When it’s done, he asks the barber how much he owes.
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“All free, friend. I consider it a service to God”.
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The next morning when the barber goes to work, he sees a bunch of flowers and a Bible in the doorstep. The flowers come with a thank you card from the priest.
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Presently, a policeman enters, wanting a trim. When the barber is finished, the policeman asks how much he owes.
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“No charge, friend. I consider this a service to the Lord above”.
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The next day when the barber turns up to work, there’s a box of donuts and a thank you card on the doorstep.
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In the afternoon, a senator comes in for a haircut. When the barber is finished, he tells the surprised but pleased senator that there is no charge, as he considers it a service to God.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
When the barber goes to work the next day, there’s a line of senators waiting in a long line for haircuts.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/Arkady2009"> /u/Arkady2009 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/wsd2zb/a_priest_goes_to_the_barber_for_a_haircut/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/wsd2zb/a_priest_goes_to_the_barber_for_a_haircut/">[comments]</a></span></p></li>
<li><strong>A married man keeps telling his wife “ Honey , you have such a</strong> - <!-- SC_OFF -->
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“Honey, you have such a beautiful butt”
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Every person in the town agrees that she does have a very beautiful butt. The man’s birthday is coming up so she decides to take a trip to the tattoo parlor and get the words “Beautiful butt” tattooed on her ass.
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
She walks in and tells the tattoo artist he husband thinks she has a beautiful butt. He looks and says, “You do have a beautiful butt”. She then tells the man she wants Beautiful butt tattooed on her ass. The man tells her "I can’t fit that on your ass, it takes up too much space. But I tell you what, I will tattoo the letters BB on each cheek and that can stand for beautiful butt. She agrees and gets it done.
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On the man’s birthday she hears him come home and is only wearing a robe. She then stands at the top of the stairs. He opens the door and she says “look honey.” She then takes off the robe she is wearing, bends over, and the man yells “WHO THE FUCK IS BOB?”!
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"> submitted by <a href="https://www.reddit.com/user/nikan69"> /u/nikan69 </a> <br/> <span><a href="https://www.reddit.com/r/Jokes/comments/wswvx9/a_married_man_keeps_telling_his_wife_honey_you/">[link]</a></span> <span><a href="https://www.reddit.com/r/Jokes/comments/wswvx9/a_married_man_keeps_telling_his_wife_honey_you/">[comments]</a></span></p></li>
</ul>
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