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184 lines
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<title>26 July, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Mammalian cells-based platforms for the generation of SARS-CoV-2 virus-like particles</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19. Though many COVID-19 vaccines have been developed, most of them are delivered via intramuscular injection and thus confer relatively weak mucosal immunity against the natural infection. Virus-Like Particles (VLPs) are self-assembled nanostructures composed of key viral structural proteins, that mimic the wild-type virus structure but are non-infectious and non-replicating due to the lack of viral genetic material. In this study, we efficiently generated SARS-CoV-2 VLPs by co-expressing the four SARS-CoV-2 structural proteins, specifically the membrane (M), small envelope (E), spike (S) and nucleocapsid (N) proteins. We show that these proteins are essential and sufficient for the efficient formation and release of SARS-CoV-2 VLPs. Moreover, we used lentiviral vectors to generate human cell lines that stably produce VLPs. Because VLPs can bind to the virus natural receptors, hence leading to entry into cells and viral antigen presentation, this platform could be used to develop novel vaccine candidates that are delivered intranasally.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550415v1" target="_blank">Mammalian cells-based platforms for the generation of SARS-CoV-2 virus-like particles</a>
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</div></li>
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<li><strong>Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in SARS-CoV-2 and Its Variants</strong> -
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<div>
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Background: Host response is critical to the onset, progression, and outcome of viral infections. Since viruses hijack the host cellular metabolism for their replications, we hypothesized that restoring host cell metabolism can efficiently reduce viral production. Here, we present a viral-host Metabolic Modeling (vhMM) method to systematically evaluate the disturbances in host metabolism in viral infection and computationally identify targets for modulation by integrating genome-wide precision metabolic modeling and cheminformatics. Results: In SARS-CoV-2 infections, we identified consistent changes in host metabolism and gene and endogenous metabolite targets between the original SARS-COV-2 and different variants (Alpha, Delta, and Omicron). Among six compounds predicted for repurposing, methotrexate, cinnamaldehyde, and deferiprone were tested in vitro and effective in inhibiting viral production with IC50 less than 4uM. Further, an analysis of real-world patient data showed that cinnamon usage significantly reduced the SARS-CoV-2 infection rate with an odds ratio of 0.65 [95%CI: 0.55~0.75]. Conclusions: These results demonstrated that vhMM is an efficient method for predicting targets and drugs for viral infections.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550423v1" target="_blank">Predictive Systems Biology Modeling: Unraveling Host Metabolic Disruptions and Potential Drug Targets in SARS-CoV-2 and Its Variants</a>
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</div></li>
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<li><strong>Real-time Dissection and Forecast of Infection Dynamics during a Pandemic</strong> -
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<div>
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Pandemic preparedness requires institutions, including public health authorities and governments, to detect, survey and control outbreaks. To maintain an accurate, quantitative and up-to-date picture of an epidemic crisis is key. For SARS-CoV-2, this was mostly achieved by ascertaining incidence numbers and the effective reproductive number (R_eff), which counts how many people an infected person is likely to infect on average. These numbers give strong hints on past infection dynamics in a population but fail to clearly characterize current and future dynamics as well as potential effects of pharmaceutical and non-pharmaceutical interventions. We show that, by using and combining infection surveillance and population-scale contact statistics, we can obtain a better understanding of the drivers of epidemic waves and the effectiveness of interventions. This approach can provide a real-time picture, thus saving not only many lives by quickly allowing adaptation of the health policies but also alleviating economic and other burdens if an intervention proves ineffective. We factorize R_eff into contacts and relative transmissibility: Both signals can be used, individually and combined, to identify driving forces of an epidemic, monitoring and assessing interventions, as well as projecting an epidemic9s future trajectory. Using data for SARS-CoV-2 and Influenza from 2019 onward in Germany, we provide evidence for the usefulness of our approach. In particular, we find that the effects from physical distancing and lockdowns as well as vaccination campaigns are dominant.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.03.02.23286502v3" target="_blank">Real-time Dissection and Forecast of Infection Dynamics during a Pandemic</a>
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</div></li>
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<li><strong>Lineage replacement and evolution captured by the United Kingdom Covid Infection Survey</strong> -
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<div>
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The Office for National Statistics COVID-19 Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterised by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens, particularly in the current phase of the pandemic with routine RT-PCR testing now ended in the community.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.05.21268323v2" target="_blank">Lineage replacement and evolution captured by the United Kingdom Covid Infection Survey</a>
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</div></li>
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<li><strong>A low-cost molecular test for SARS-CoV-2 detection suitable for variant discrimination and community testing using saliva</strong> -
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The gold standard for COVID-19 diagnostic testing relies on RNA extraction from naso/oropharyngeal swab followed by amplification through RT-PCR with fluorogenic probes. While the test is extremely sensitive and specific, its high cost and the potential discomfort associated with specimen collection make it suboptimal for public health screening purposes. In this study, we developed an equally reliable, but cheaper and less invasive alternative test based on a one-step RT-PCR with the DNA-intercalating dye SYBR Green, which enables the detection of SARS-CoV-2 directly from saliva samples or RNA isolated from nasopharyngeal swabs. Importantly, we found that this type of testing can be fine-tuned to discriminate SARS-CoV-2 variants of concern. The saliva RT-PCR SYBR Green test was successfully used in a mass-screening initiative targeting nearly 4500 asymptomatic children under the age of 12. Testing was performed at a reasonable cost of less than € 0.8 per child, and in some cases, the saliva test outperformed nasopharyngeal rapid antigen tests in identifying infected children. Whole genome sequencing revealed that the antigen testing failure could not be attributed to a specific lineage of SARS-CoV-2. To further reduce testing costs, we produced all the necessary enzymes and established a new RT-PCR protocol based on the EvaGreen dye. Overall, this work strongly supports the view that RT-PCR saliva tests based on DNA-intercalating dyes represent a powerful strategy for community screening of SARS-CoV-2. The tests can be easily applied to other infectious agents and, therefore, constitute a powerful resource for an effective response to future pandemics.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.20.23292863v1" target="_blank">A low-cost molecular test for SARS-CoV-2 detection suitable for variant discrimination and community testing using saliva</a>
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</div></li>
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<li><strong>Prevalence, determinants, and trends in the experience and perpetration of intimate partner violence among a cohort of gay, bisexual, and other men who have sex with men in Montréal, Toronto, and Vancouver, Canada (2017-2022)</strong> -
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Purpose: Longitudinal data on the experience and perpetration of intimate partner violence (IPV) among gay, bisexual, and other men who have sex with men (GBM) is limited. We estimated the prevalence of past six-month (P6M) physical and/or sexual IPV (hereafter IPV) experience and perpetration, identified their determinants, and assessed temporal trends, including the impact of the COVID-19 pandemic. Methods: We used data from the Engage Cohort Study (2017-2022) of GBM recruited using respondent-driven sampling in Montréal, Toronto, and Vancouver. Adjusted prevalence ratios (aPR) for determinants and self-reported P6M IPV were estimated using generalized estimating equations, accounting for attrition (inverse probability of censoring weights) and relevant covariates. Longitudinal trends of IPV were also assessed. Results: Between 2017-2022, 1,455 partnered GBM (median age 32 years, 82% gay, and 71% white) had at least one follow-up visit. Baseline proportions were 31% for lifetime IPV experience and 17% for lifetime perpetration. During follow-up, P6M IPV experience was more common (6%, 95%CI: 5-7%) than perpetration (4%, 95%CI: 3-5%). Factors associated with P6M IPV experience include prior IPV experience (aPR=2.79, 95%CI: 1.83-4.27), less education (aPR=2.08, 95%CI: 1.14-3.79), and substance use (injection aPR=5.68, 95%CI: 2.92-11.54, non-injection aPR=1.70, 95%CI: 1.05-2.76). Similar factors were associated with IPV perpetration. IPV was stable over time; periods of COVID-19 restrictions were not associated with IPV changes in this cohort. Conclusion: Prevalence of IPV was high among GBM. Determinants related to marginalization are associated with an increased risk of IPV. Interventions should address these determinants to reduce IPV and improve health.
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</p>
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.24.23293112v1" target="_blank">Prevalence, determinants, and trends in the experience and perpetration of intimate partner violence among a cohort of gay, bisexual, and other men who have sex with men in Montréal, Toronto, and Vancouver, Canada (2017-2022)</a>
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<li><strong>Quantification of Covid-19 Vaccine Coercion in India: A Survey Study</strong> -
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Introduction: Informed consent is the cornerstone of medical ethics, enshrined in the constitution of most countries, as well as in international documents. However, mandates for Covid-19 vaccination as well as coercion was prevalent in many places in the world, including in India. Against this background, we did a cross sectional study to assess and quantify the extent of Covid-19 vaccine coercion in India. Methods: A cross sectional study was conducted after obtaining ethical clearance from IIT Bombay. This survey was conducted using a pretested questionnaire anonymously amongst the college students and adults in Mumbai from October 2022 to December 2022. The questionnaire contained details of why the vaccine was taken, and if the participant was a student. Descriptive analysis was conducted and frequencies, percentages along with 95% confidence intervals were used to summarize the findings. Results: A total of 483 participants responded, which included both students and non students, of which 470 participants reported having taken the vaccine. A total of 106 (21.95%, 95% C.I. 18.48% to 25.85%) reported to have pressured into taking the vaccine. The level of coercion was similar among college students 78 (21.61%, 95% C.I. 17.67% to 26.14%) and non student adults 28 (22.95%, 95% C.I. 15.82% to 31.43%). Conclusion: A significant proportion was coerced into taking the vaccines, violating the requirement for informed consent. These results are of paramount importance for future policies as well as for posterity.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.24.23293089v1" target="_blank">Quantification of Covid-19 Vaccine Coercion in India: A Survey Study</a>
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</div></li>
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<li><strong>The Impact of Nontransparent Health Communication During the COVID-19 Pandemic on Vaccine- Hesitant People’s Perception of Vaccines</strong> -
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<div>
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Although transparency is crucial for building public trust, public health communication during the COVID-19 pandemic was often nontransparent. In a cross-sectional online study with COVID-19 vaccine-hesitant German residents (N = 763), we explored the impact of COVID-19 public health communication on the attitudes of vaccine-hesitant individuals towards vaccines as well as their perceptions of incomprehensible and incomplete information. We also investigated whether specific formats of public health messaging were perceived as more trustworthy. Of the 763 participants, 90 (11.8%) said they had become more open-minded towards vaccines in general, 408 (53.5%) reported no change, and 265 (34.7%) said they had become more skeptical as a result of public health communication on COVID-19 vaccines. These subgroups differed in how incomprehensible they found public health communication and whether they thought information had been missing. Participants’ ranking of trustworthy public health messaging did not provide clear-cut results: the fully transparent message, which reported the benefit and harms in terms of absolute risk, and the nontransparent message, which reported only the benefit in terms of relative risk were both considered equally trustworthy (p = .848). Increased skepticism about vaccines during the COVID-19 pandemic may have partly been fueled by subpar public health communication. Given the importance of public trust for coping with future health crises, public health communicators should ensure that their messaging is clear and transparent.
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🖺 Full Text HTML: <a href="https://osf.io/znwyx/" target="_blank">The Impact of Nontransparent Health Communication During the COVID-19 Pandemic on Vaccine- Hesitant People’s Perception of Vaccines</a>
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<li><strong>Comprehensive analysis of next-generation sequencing data in COVID-19 and its secondary complications</strong> -
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The ongoing pandemic of coronavirus disease 2019 (COVID-19) has made a serious public health threat globally. To discover key molecular changes in COVID-19 and its secondary complications, we analyzed next-generation sequencing (NGS) data of COVID-19. NGS data (GSE163151) was screened and downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were identified in the present study, using DESeq2 package in R programming software. Gene ontology (GO) and pathway enrichment analysis were performed, and the protein-protein interaction (PPI) network, module analysis, miRNA-hub gene regulatory network and TF-hub gene regulatory network were established. Subsequently, receiver operating characteristic curve (ROC) analysis was used to validate the diagonostics valuesof the hub genes. Firstly, 954 DEGs (477 up regulated and 477 down regulated) were identified from the four NGS dataset. GO enrichment analysis revealed enrichment of DEGs in genes related to the immune system process and multicellular organismal process, and REACTOME pathway enrichment analysis showed enrichment of DEGs in the immune system and formation of the cornified envelope. Hub genes were identified from the PPI network, module analysis, miRNA-hub gene regulatory network and TF-hub gene regulatory network. Furthermore, the ROC analysis indicate that COVID-19 and its secondary complications with following hub genes, namely, RPL10, FYN, FLNA, EEF1A1, UBA52, BMI1, ACTN2, CRMP1, TRIM42 and PTCH1, had good diagnostics values. This study identified several genes associated with COVID-19 and its secondary complications, which improves our knowledge of the disease mechanism.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.02.03.478930v2" target="_blank">Comprehensive analysis of next-generation sequencing data in COVID-19 and its secondary complications</a>
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<li><strong>Reduced Olfactory Bulb Volume Accompanies Olfactory Dysfunction After Mild SARS-CoV-2 Infection</strong> -
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Background: Despite its high prevalence, the determinants of smelling impairment in COVID-19 remain not fully understood. In this work, we aimed to examine the association between olfactory bulb volume and the clinical trajectory of COVID-19-related smelling impairment in a large-scale magnetic resonance imaging (MRI) analysis. Methodology/Principal: Data of non-vaccinated COVID-19 convalescents recruited within the framework of the Hamburg City Health Study COVID Program between March and December 2020 were analyzed. On average 8 months after recruitment, participants underwent MRI and neuropsychological testing as well as a structured questionnaire for olfactory function. Between March and April 2022 olfactory function was assessed at an additional timepoint including quantitative olfactometric testing with Sniffin Sticks. Results: This study included 233 individuals recovered from mainly mild to moderate SARS-CoV-2 infections. Longitudinal assessment demonstrated a declining prevalence of olfactory dysfunction from 67.1% at acute infection, 21.0% at baseline examination and 17.5% at follow-up. Participants with post-acute olfactory dysfunction had a significantly lower olfactory bulb volume at scan-time than normally smelling individuals. Olfactory bulb volume predicted olfactometric scores at follow-up. Performance in neuropsychological testing was not significantly associated with the olfactory bulb volume. Conclusions: Our work demonstrates an association of long-term smelling dysfunction and olfactory bulb integrity in a sample of individuals recovered from mainly mild to moderate COVID-19. Collectively, our results highlight olfactory bulb volume as a surrogate marker that may inform diagnosis and guide rehabilitation strategies in COVID-19.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.24.22277973v3" target="_blank">Reduced Olfactory Bulb Volume Accompanies Olfactory Dysfunction After Mild SARS-CoV-2 Infection</a>
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<li><strong>The use and acceptability of preprints in health and social care settings: a scoping review</strong> -
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Background: Preprints are open and accessible scientific manuscript or report that is shared publicly, through a preprint server, before being submitted to a journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The scoping review explored the current evidence on the use and acceptability of preprints in health and social care settings by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nug4p/" target="_blank">The use and acceptability of preprints in health and social care settings: a scoping review</a>
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<li><strong>Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2</strong> -
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SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex consisting of nsp12, nsp7, and nsp8 as the key enzyme for viral genome replication and is a proven antiviral drug target. In this study, molecular interactions of nsp7 and nsp8 with nsp12 and the active site of nsp12 were coterminously targeted using in-silico screening of small molecule libraries to identify potential antivirals. Surface plasmon resonance (SPR) based assay using purified nsp7 and nsp8 proteins was developed, and the binding of identified molecules to targets was validated. The antiviral efficacy of identified small molecules was evaluated using cell-based assays, and potent antiviral effect with EC50 values of 0.56 uM, 0.73 uM, and 2.8 uM was demonstrated by fangchinoline, cepharanthine, and sennoside B, respectively. Further in vivo, investigation using hACE2 mice is being conducted. This is the first study that targets multiple sites in the RdRp complex of SARS-CoV-2 using a structure-based molecular repurposing approach and suggests potential therapeutic options for emerging variants of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550324v1" target="_blank">Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2</a>
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<li><strong>Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice</strong> -
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Endothelial damage and vascular pathology have been recognized as major features of COVID-19 since the beginning of the pandemic. Two main theories regarding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) damages endothelial cells and causes vascular pathology have been proposed: direct viral infection of endothelial cells or indirect damage mediated by circulating inflammatory molecules and immune mechanisms. However, these proposed mechanisms remain largely untested in vivo. Here, we utilized a set of new mouse genetic tools1 developed in our lab to test both the necessity and sufficiency of endothelial human angiotensin-converting enzyme 2 (hACE2) in COVID19 pathogenesis. Our results demonstrate that endothelial ACE2 and direct infection of vascular endothelial cells does not contribute significantly to the diverse vascular pathology associated with COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550352v1" target="_blank">Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice</a>
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<li><strong>Biophysical principles predict fitness of SARS-CoV-2 variants</strong> -
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SARS-CoV-2 is under constant selective pressure from antibodies while requiring efficient binding to host cells for successful infection. Here we focus specifically on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, a key determinant of viral entry into host cells. Through a comprehensive approach, comprising large-scale sequence analysis of SARS-CoV-2 variants and the formulation of a fitness function based on protein folding and binding thermodynamics, we unravel the relationship between the epidemiological fitness contribution of the RBD and its biophysical properties. We developed a biophysical model mapping the phenotype space, characterized by binding constants to cell receptors and antibodies, onto the fitness landscape for variants ranging from the ancestral Wuhan Hu-1 to the Omicron BA.1 . Using equilibrium statistical mechanics, we show how fitness can be expressed as a function of binding constants to cell receptors and antibodies and validate our findings through experimentally measured binding affinities and population data on frequencies of variants. This forms the basis for a comprehensive epistatic map, relating the genotype space to fitness. Our study thus delivers a tool for predicting the fitness of variants harboring previously unseen mutations, and sheds light on the impact of specific mutations on viral fitness. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.23.549087v1" target="_blank">Biophysical principles predict fitness of SARS-CoV-2 variants</a>
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<li><strong>AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</strong> -
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Metagenomic profiling algorithms commonly rely on genomic differences between lineages, strains or species to infer the relative abundances of sequences present in a sample. This observation plays an important role in the analysis of diverse microbial communities, where targeted sequencing of 16S and 18S rRNA, both well-known hypervariable genomic regions, have led to insights in microbial diversity and the discovery of novel organisms. However, the variable nature of discriminatory regions can also act as a double-edged sword, as the sought after variability can make it difficult to design primers for their amplification through PCR. Moreover, the most variable regions are not necessarily the most informative regions for the purpose of differentiation; one should focus on regions which maximize the number of lineages that can be distinguished. Here we present AmpliDiff, a computational tool that simultaneously finds such highly discriminatory genomic regions, as well as primers allowing for the amplification of these regions. We show that regions and primers found by AmpliDiff can be used to accurately estimate relative abundances of SARS-CoV-2 lineages, for example in wastewater sequencing data. We obtain mean absolute prediction errors that are comparable with using whole genome information to estimate relative abundances. Furthermore, our results show that AmpliDiff is robust against incomplete input data, and that primers designed by AmpliDiff continue to bind to genomes originating from months after the primers were selected. With AmpliDiff we provide an effective and efficient alternative to whole genome sequencing for estimating lineage abundances in viral metagenomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.22.550164v1" target="_blank">AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: theophylline; Drug: Placebo<br/><b>Sponsor</b>: Washington University School of Medicine<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Lymph node aspiration / Blood sampling<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: MVA-SARS-2-S; Other: Placebo<br/><b>Sponsors</b>: Universitätsklinikum Hamburg-Eppendorf; German Center for Infection Research; Philipps University Marburg Medical Center; Ludwig-Maximilians - University of Munich; University Hospital Tuebingen; CTC-NORTH<br/><b>Withdrawn</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Treatment of Long COVID (TLC) Feasibility Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Low-dose Naltrexone (LDN); Drug: Cetirizine; Drug: Famotidine; Drug: LDN Placebo; Drug: Cetirizine Placebo; Drug: Famotidine Placebo<br/><b>Sponsors</b>: Emory University; CURE Drug Repurposing Collaboratory (CDRC)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome</strong> - <b>Conditions</b>: Fatigue; Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Procedure: Immunoadsorption vs. sham immunoadsorption<br/><b>Sponsor</b>: Hannover Medical School<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Non-ventilated Prone Positioning in the COVID-19 Population</strong> - <b>Conditions</b>: COVID-19; Proning; Oxygenation; Length of Stay<br/><b>Interventions</b>: Other: Proning group; Other: Control group<br/><b>Sponsor</b>: Baylor St. Luke’s Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS).</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Cognitive Impairment; Neurological Complication<br/><b>Intervention</b>: Drug: VIX001<br/><b>Sponsor</b>: Neobiosis, LLC<br/><b>Not yet recruiting</b></p></li>
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<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 on the Safety and Immune Response of a Booster Dose of Investigational COVID-19 mRNA Vaccines in Healthy Adults</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: CV0701 Bivalent High dose; Biological: CV0701 Bivalent Medium dose; Biological: CV0701 Bivalent Low dose; Biological: CV0601 Monovalent High dose; Biological: Control vaccine<br/><b>Sponsors</b>: GlaxoSmithKline; CureVac<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Drug: Upamostat; Drug: Placebo (PO)<br/><b>Sponsors</b>: Henry M. Jackson Foundation for the Advancement of Military Medicine; Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies; FHI Clinical, Inc.; RedHill Biopharma Limited<br/><b>Not yet recruiting</b></p></li>
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<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 Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression</strong> - <b>Conditions</b>: COVID 19 Disease; Mild to Moderate COVID 19 Disease; SARS-CoV-2; Infectious Disease; Severe Acute Respiratory Syndrome Coronavirus 2<br/><b>Interventions</b>: Drug: Tafenoquine Oral Tablet; Drug: Placebo<br/><b>Sponsor</b>: 60P Australia Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<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 to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>: Drug: MBS-COV; Drug: Placebo<br/><b>Sponsor</b>: Oneness Biotech Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of Covid 19 on Sinus Augmentation Surgery</strong> - <b>Condition</b>: Bone Loss<br/><b>Interventions</b>: Procedure: Sinus lift in patients with COVID-19 history; Procedure: Sinus lift with no COVID-19 history<br/><b>Sponsor</b>: Cairo University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MR-spectroscopy in Post-covid Condition Prior to and Following a Yoga Breathing Intervention</strong> - <b>Conditions</b>: Post COVID-19 Condition; Somatic Symptom Disorder<br/><b>Interventions</b>: Behavioral: yoga; Behavioral: social contact<br/><b>Sponsor</b>: Medical University Innsbruck<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Clinical Evaluation of SARS-COV-2 (COVID-19), Influenza and RSV 8-Well MT-PCR Panel for In Vitro Diagnostics</strong> - <b>Condition</b>: Respiratory Viral Infection<br/><b>Interventions</b>: Diagnostic Test: SARS-COV-2, Influenza and RSV 8-Well MT-PCR Panel; Diagnostic Test: BioFire Respiratory Panel 2.1<br/><b>Sponsor</b>: AusDiagnostics Pty Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expressive Interviewing Agents to Support Health-Related Behavior Change</strong> - <b>Condition</b>: Mental Stress<br/><b>Intervention</b>: Other: Expressive Interviewing<br/><b>Sponsors</b>: University of Michigan; University of Texas at Austin<br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Chemoinformatics approach to design and develop vanillin analogs as COX-1 inhibitor</strong> - CONCLUSION: In comparison to other vanillin derivative compounds, 4-formyl-2-methoxyphenyl benzoate has the lowest binding energy value; hence, this analog can continue to be synthesized and its potential as an antithrombotic agent might be confirmed by in vivo studies.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Korean Red Ginseng Relieves Inflammation and Modulates Immune Response Induced by Pseudo-Type SARS-CoV-2</strong> - Few studies have reported the therapeutic effects of Korean red ginseng (KRG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the positive effects of KRG on other viruses have been reported and the effects of KRG on pulmonary inflammatory diseases have also been studied. Therefore, this study investigated the therapeutic effects of KRG-water extract (KRG-WE) in a pseudo-type SARS-CoV-2 (PSV)-induced lung injury model. Constructing the pseudovirus, human…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Vector-delivered artificial miRNA effectively inhibits Porcine epidemic diarrhea virus replication</strong> - CONCLUSIONS: In summary, these results suggest that an RNAi based on amiRNA targeting the conserved region of the virus is an effective method to improve PEDV nucleic acid inhibitors and provide a novel treatment strategy for PEDV infection.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Deciphering the role of fucoidan from brown macroalgae in inhibiting SARS-CoV-2 by targeting its main protease and receptor binding domain: Invitro and insilico approach</strong> - The current study investigated the role of fucoidan from Padina tetrastromatica and Turbinaria conoides against 3-chymotrypsin like protease (3CL^(pro)) and receptor binding domain (RBD) spike protein of SARS-CoV-2 using an invitro and computational approach. The 3CL^(pro) and RBD genes were successfully cloned in pET28a vector, expressed in BL-21DE3 E. coli rosetta cells and purified by ion exchange affinity and size exclusion chromatography. Fucoidan extracted from both biomass using green…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases</strong> - Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy</strong> - SARS-CoV-2 (COVID-19) exerts profound changes in the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism that may underpin its pathophysiology. The KP is the main source of the vital cellular effector NAD+ and intermediate metabolites that modulate immune and neuronal functions. Trp metabolism is the top pathway influenced by COVID-19. Sixteen studies established virus-induced activation of the KP mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO1) in most affected…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Regulation of autophagy by SARS-CoV-2: The multifunctional contributions of ORF3a</strong> - Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) regulates autophagic flux by blocking the fusion of autophagosomes with lysosomes, causing the accumulation of membranous vesicles for replication. Multiple SARS-CoV-2 proteins regulate autophagy with significant roles attributed to ORF3a. Mechanistically, open reading frame 3a (ORF3a) forms a complex with UV radiation resistance associated, regulating the functions of the PIK3C3-1 and PIK3C3-2 lipid kinase complexes, thereby…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Fangchinoline inhibits the PEDV replication in intestinal epithelial cells via autophagic flux suppression</strong> - Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world’s swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Silver N-heterocyclic carbene complexes are potent uncompetitive inhibitors of the papain-like protease with antiviral activity against SARS-CoV-2</strong> - The ongoing SARS-CoV-2 pandemic has caused a high demand for novel innovative antiviral drug candidates. Despite promising results, metal complexes have been relatively unexplored as antiviral agents in general and in particular against SARS-CoV-2. Here we report on silver NHC complexes with chloride or iodide counter ligands that are potent inhibitors of the SARS-CoV-2 papain-like protease (PL^(pro)) but inactive against 3C-like protease (3CL^(pro)) as another SARS-CoV-2 protease. Mechanistic…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Nanoparticle approaches for the renin-angiotensin system</strong> - The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin</strong> - Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC(50) values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC(50) value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>One master and two servants: One Zr(Ⅳ) with two ligands of TCPP and NH<sub>2</sub>-BDC form the MOF as the electrochemiluminescence emitter for the biosensing application</strong> - Here we put forward an innovative “one master and two servants” strategy for enhancing the ECL performance. A novel ECL luminophore named Zr-TCPP/NH(2)-BDC (TCPP@UiO-66-NH(2)) was synthesized by self-assembly of meso-tetra(4-carboxyphenyl)porphine (TCPP) and 4-aminobenzoic acid (NH(2)-BDC) with Zr clusters. TCPP@UiO-66-NH(2) has a porous structure and a highly ordered structure, which allows the molecular motion of TCPP to be effectively confined, thereby inhibiting nonradiative energy transfer….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications</strong> - Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer. These ionizable lipids have unique…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX</strong> - In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline’s ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (M^(pro)) and papain-like…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants</strong> - Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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