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174 lines
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<title>14 September, 2022</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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<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>IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques</strong> -
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<div>
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The pro- and anti-inflammatory pathways that determine the balance of inflammation and viral control during SARS-CoV-2 infection are not well understood. Here we examine the roles of IFN{gamma} and IL-10 in regulating inflammation, immune cell responses and viral replication during SARS-CoV-2 infection of rhesus macaques. IFN{gamma} blockade tended to decrease lung inflammation based on 18FDG-PET/CT imaging but had no major impact on innate lymphocytes, neutralizing antibodies, or antigen-specific T cells. In contrast, IL-10 blockade transiently increased lung inflammation and enhanced accumulation of virus-specific T cells in the lower airways. However, IL-10 blockade also inhibited the differentiation of virus-specific T cells into airway CD69+CD103+ TRM cells. While virus-specific T cells were undetectable in the nasal mucosa of all groups, IL-10 blockade similarly reduced the frequency of total TRM cells in the nasal mucosa. Neither cytokine blockade substantially affected viral load and infection ultimately resolved. Thus, in the macaque model of mild COVID-19, the pro- and anti-inflammatory effects of IFN{gamma} and IL-10 have no major role in control of viral replication. However, IL-10 has a key role in suppressing the accumulation of SARS-CoV-2-specific T cells in the lower airways, while also promoting TRM at respiratory mucosal surfaces.
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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/10.1101/2022.09.13.507852v1" target="_blank">IL-10 suppresses T cell expansion while promoting tissue-resident memory cell formation during SARS-CoV-2 infection in rhesus macaques</a>
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</div></li>
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<li><strong>Does Vaping Increase the Likelihood of SARS-CoV-2 Infection? Paradoxically Yes and No</strong> -
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Data on the relationship between electronic cigarettes (ECs) and SARS-CoV-2 infection are limited and contradictory. Evidence indicates that EC aerosols or nicotine increase ACE2, SARS-CoV-2 virus receptors, which increase virus binding and susceptibility. Our objectives were to determine if EC aerosols increased SARS-CoV-2 infection of human bronchial epithelial cells and to identify the causative chemical(s). A 3D organotypic model (EpiAirway) in conjunction with air liquid interface (ALI) exposure was used to test the effects of aerosols produced from JUUL Virginia Tobacco and BLU ECs, or individual chemicals (nicotine, propylene glycol, vegetable glycerin (PG/VG), and benzoic acid) on infection using SARS-CoV-2 pseudoparticles. Exposure of EpiAirway to JUUL aerosols increased ACE2, while BLU and lab-made EC aerosols containing nicotine increased ACE2 levels and TMPRSS2 activity, a spike protease that enables viral-cell fusion. Pseudoparticle infection of EpiAirway increased with aerosols produced from PG/VG, PG/VG plus nicotine, or BLU ECs. JUUL EC aerosols did not increase infection above controls. The baseline level of infection in JUUL treated aerosol groups was attributed to benzoic acid, which mitigated the enhanced infection caused by PG/VG or nicotine. The benzoic acid protection from enhanced infection continued at least 48 hours after exposure. TMPRSS2 activity was significantly correlated with e-liquid pH, which in turn was significantly correlated with infection, with lower pH blocking PG/VG and nicotine-induced-enhanced infection. While ACE2 levels increased in EpiAirway tissues exposed to EC aerosols, infection depended on the ingredients of the e-liquids. PG/VG and nicotine enhanced infection, an effect that was mitigated by benzoic acid.
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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/10.1101/2022.09.09.507373v1" target="_blank">Does Vaping Increase the Likelihood of SARS-CoV-2 Infection? Paradoxically Yes and No</a>
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<li><strong>Monitoring correlates of SARS-CoV-2 infection in cell culture using two-photon microscopy and a novel fluorescent calcium-sensitive dye</strong> -
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The organism-wide effects of viral infection SARS-CoV-2 are well studied, but little is known about the dynamics of how the infection spreads in time among or within cells due to the scarcity of suitable high-resolution experimental systems. Two-photon (2P) imaging combined with a proper subcellular staining technique has been an effective tool for studying mechanisms at such resolutions and organelle levels. Herein, we report the development of a novel calcium sensor molecule along with a 2P-technique for identifying imaging patterns associated with cellular correlates of infection damage within the cells. The method works as a cell viability assay and also provides valuable information on how the calcium level and intracellular distribution are perturbed by the virus. Moreover, it allows the quantitative analysis of infection dynamics. This novel approach facilitates the study of the infection progression and the quantification of the effects caused by viral variants and viral load.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.12.506773v1" target="_blank">Monitoring correlates of SARS-CoV-2 infection in cell culture using two-photon microscopy and a novel fluorescent calcium-sensitive dye</a>
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<li><strong>Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant</strong> -
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The emergence of SARS-CoV-2 variants in the Omicron lineage with large number of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains.
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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/10.1101/2022.09.12.507614v1" target="_blank">Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant</a>
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<li><strong>Humoral immunogenicity of a Coronavirus Disease 2019 (COVID-19) DNA Vaccine in Rhesus Macaques (Macaca mulatta) Delivered using Needle-free Jet Injection</strong> -
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A SARS-CoV-2 DNA vaccine targeting the spike protein and delivered by jet injection, nCOV-S(JET), previously shown to protect wild-type and immunosuppressed Syrian hamsters (Mesocricetus auratus), was evaluated via two needle-free delivery methods in rhesus macaques (Macaca mulatta). The methods included intramuscular delivery of 2 mg per vaccination with the PharmaJet Stratis device and intradermal delivery of 0.4 mg per vaccination with the PharmaJet Tropis device. We hypothesized that the nCOV-S(JET) vaccine would mount detectable neutralizing antibody responses when delivered by needle-free jet injection by either the intradermal or intramuscular route. When delivered intramuscularly, the vaccines elicited neutralizing and variant (Beta, Gamma, and Delta) cross-neutralizing antibodies against SARS-CoV-2 in all six animals after three vaccinations. When delivered at a lower dose by the intradermal route, strong neutralizing antibody responses were only detected in two of six animals. This study confirms that a vaccine previously shown to protect in a hamster model can elicit neutralizing and cross-neutralizing antibodies against SARS-CoV-2 in nonhuman primates. We posit that nCOV-S(JET) has the potential for use as booster vaccine in heterologous vaccination strategies against COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.12.507647v1" target="_blank">Humoral immunogenicity of a Coronavirus Disease 2019 (COVID-19) DNA Vaccine in Rhesus Macaques (Macaca mulatta) Delivered using Needle-free Jet Injection</a>
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<li><strong>Comparative multi-OMICS single-cell atlas of five COVID-19 (rAdVV and mRNA) vaccines describe unique and distinct mechanisms of action</strong> -
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COVID-19 vaccines based on a range of expression platforms have shown considerable protective efficacy, generating antibody and T cell immune responses. However, molecular pathways underpinning the COVID-19 vaccine priming of immunity against the SARS-CoV-2 virus have not yet been explored extensively. This analysis is critical to the optimization of future vaccination strategies, schedules, and combinations. Thus, we investigated a cohort of individuals pre- and post-vaccination to understand the humoral and cellular immune response against different COVID-19 vaccines, including recombinant adenoviral vector (rAdVV) and mRNA-based vaccines. Single-cell RNA sequencing allowed characterization of monocytes, T, NK and B cell activation at the transcriptomics/proteomic level, in response to different COVID-19 vaccines. Our data revealed that different COVID-19 vaccines elicit a unique and distinct mechanism of action. Specifically, we revealed that rAdVV vaccines negatively regulate CD4+ T cell activation, leukocytes chemotaxis, IL-18 signalling and antigen presentation by monocytes whilst mRNA vaccines positively regulate NKT cell activation, platelets activation and chemokine signalling pathways. An antigen-specific T cell response was already observed following the 1st vaccine dose and was not further augmented after the subsequent 2nd dose of the same vaccine and it was dependent on the type of vaccination used. Our integrated three layered-analyses highlights that COVID-19 vaccines evoke a strong but divergent immune response at the RNA, protein, and cellular levels. Our approach is able to pinpoint efficacy and mechanisms controlling immunity to vaccination and open the door for better vaccination which could induce innate and adaptive immunity equally in the long term.
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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/10.1101/2022.09.12.507666v1" target="_blank">Comparative multi-OMICS single-cell atlas of five COVID-19 (rAdVV and mRNA) vaccines describe unique and distinct mechanisms of action</a>
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<li><strong>Evaluation of endogenous and therapeutic 25-hydroxycholesterols in murine models of pulmonary SARS-CoV-2 infection</strong> -
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Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-hydroxycholesterol (25HC), a product of activity of cholesterol-25-hydroxylase (CH25H) upon cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against SARS-CoV-2. However, 25HC can also amplify inflammation and tissue injury and be converted by CYP7B1 to 7,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro studies and two different murine models of SARS-CoV-2 infection, we investigate the effects of these two oxysterols on SARS-CoV-2 pneumonia. We show that while 25HC and enantiomeric-25HC are antiviral in vitro against human endemic coronavirus-229E, they did not inhibit SARS-CoV-2; nor did supplemental 25HC reduce pulmonary SARS-CoV-2 titers in the K18-human ACE2 mouse model in vivo. 25HC treatment also did not alter immune cell influx into the airway, airspace cytokines, lung pathology, weight loss, symptoms, or survival but was associated with increased airspace albumin, an indicator of microvascular injury, and increased plasma pro-inflammatory cytokines. Conversely, mice treated with the EBI2/GPR183 inhibitor NIBR189 displayed a modest increase in lung viral load only at late time points, but no change in weight loss. Consistent with these findings, although Ch25h was upregulated in the lungs of SARS-CoV-2-infected WT mice, lung viral titers and weight loss in Ch25h-/- and Gpr183-/- mice infected with the beta variant were similar to control animals. Taken together, endogenous 25-hydroxycholesterols do not significantly regulate early SARS-CoV-2 replication or pathogenesis and supplemental 25HC may have pro-injury rather than therapeutic effects in SARS-CoV-2 pneumonia.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.12.507671v1" target="_blank">Evaluation of endogenous and therapeutic 25-hydroxycholesterols in murine models of pulmonary SARS-CoV-2 infection</a>
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<li><strong>A general theory for infectious disease dynamics.</strong> -
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We present a general theory of infection spreading, which directly follows from conservation laws and takes as inputs the probability density functions of latent times. The derivation of the theory substantially differs from Kermack and McKendrick (1927) argument, which instead was based on the concept of removal rates. We demonstrate the formal equivalence of the two approaches, but our theory provides a clear interpretation of the kernels of the integro-differential governing the infection spreading in terms of survival function of the latent times distributions. This aspect was never captured before. Real distributions of latent times can be, then, employed, thus overcoming the limitations of standard SIR, SEIR and other similar models, which implicitly make use of exponential or exponential-related distributions. SIR and SEIR-type models are, in fact, a subclass of the theory here presented. We show that beside the infection rate ν, the joint probability density function p_{EI}(τ,τ₁) of latent times in the exposed and infectious compartments governs the infection spreading. Assuming that the number of infected individuals is negligibile compare to the entire population, we where able to study the stability of the dynamical system and provide the general solution of equations in terms characteristic functions of the probability distribution of latent times. We present asymptotic solutions for the case R₀=1 and demostrate that the moments of the latent times distribution govern the rate of disease spreading in this case. The present theory is employed to simulate the diffusion of COVID-19 infection in Italy during the first 120 days. The estimated value of the basic reproduction number is R₀≈3.5, in very good agreement with existing data.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.12.22278744v1" target="_blank">A general theory for infectious disease dynamics.</a>
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<li><strong>Subjective assessment and taste strips testing of gustatory function, at home, and in the lab</strong> -
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Gustatory ability is an important marker of health status, including COVID-19 disease. We compare self-reporting with home and lab psychophysical “taste strips” tests in healthy subjects. The taste test consisted of paper strips impregnated with sweet, bitter, salty, or sour tastants, and with the trigeminal stimulus capsaicin, each in high and in low concentration. The test was carried out either in a controlled lab environment (74 participants, 47 women) with the strips being administered by the experimenter or self-administered by the participants at home (77 participants, 59 women). After self-reporting their subjective assessment of chemosensory ability, the participant identified the taste of each strip and rated intensity and pleasantness. Identification score, intensity, and pleasantness averaged over the 8 taste strips were similar between the lab and the home-administered tests. Self-rated taste ability did not correlate with any of these scores, but strongly correlated with self-rated smell ability in the lab group (r=0.73), and moderately correlated in the home group (r=0.51). Taste identification correlated with intensity ratings (r=0.63 lab, r=0.36 home) but not with the pleasantness ratings (r=-0.14 lab, r=0.1 home). The results of the taste strips test were similar in the lab and at home for healthy young participants and provide a baseline against which taste tests can be compared in future applications.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.11.507407v1" target="_blank">Subjective assessment and taste strips testing of gustatory function, at home, and in the lab</a>
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<li><strong>Data-driven multiscale dynamical framework to control a pandemic evolution with non-pharmaceutical interventions</strong> -
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Before the availability of vaccines, many countries have resorted multiple times to drastic social restrictions to prevent saturation of their health care system, and to regain control over an otherwise exponentially increasing COVID-19 pandemic. With the advent of data-sharing, computational approaches are key to efficiently control a pandemic with non-pharmaceutical interventions (NPIs). Here we develop a data-driven computational framework based on a time discrete and age-stratified compartmental model to control a pandemic evolution inside and outside hospitals in a constantly changing environment with NPIs. Besides the calendrical time, we introduce a second time-scale for the infection history, which allows for non-exponential transition probabilities. We develop inference methods and feedback procedures to successively recalibrate model parameters as new data becomes available. As a showcase, we calibrate the framework to study the pandemic evolution inside and outside hospitals in France until February 2021. We combine national hospitalization statistics from governmental websites with clinical data from a single hospital to calibrate hospitalization parameters. We infer changes in social contact matrices as a function of NPIs from positive testing and new hospitalization data. We use simulations to infer hidden pandemic properties such as the fraction of infected population, the hospitalisation probability, or the infection fatality ratio. We show how reproduction numbers and herd immunity levels depend on the underlying social dynamics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.07.28.21260870v3" target="_blank">Data-driven multiscale dynamical framework to control a pandemic evolution with non-pharmaceutical interventions</a>
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<li><strong>The Role of Non-Pharmaceutical Interventions for the Mental Health Consequences of Widowhood during the COVID-19 Pandemic</strong> -
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Spousal loss is associated with immediate declines in mental health. However, the mental health consequences of widowhood during the Covid-19 pandemic have remained largely unexplored. In this research note, we use data from the Survey of Health, Ageing, and Retirement in Europe and fixed effects regression modelling to address three research questions: (1) How has the mental health of older adults changed across time in 10 European countries? (2) Do the surviving spouses of persons who died during the pandemic face greater declines in mental health compared to adults widowed prior to the pandemic? (3) To what extent did the strictness of non-pharmaceutical interventions (NPIs) moderate the pandemic widowhood penalty for mental health? We found that feelings of depression increased dramatically for those widowed during the pandemic compared to widowed adults prior to the pandemic. In addition, the pandemic widowhood penalty does not apply to all those who lost their partners during the pandemic, but only to those who lost their partner during periods when strict NPIs were being enforced by governments. Our findings support that notion that the Covid-19 pandemic and strict NPIs exacerbated risk factors and hindered protective factors that affect older adults’ resilience to spousal death.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/2rc5s/" target="_blank">The Role of Non-Pharmaceutical Interventions for the Mental Health Consequences of Widowhood during the COVID-19 Pandemic</a>
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<li><strong>Phenotypic plasticity and the anthropause: an urban bird becomes less aggressive</strong> -
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Urban areas often impose strong, novel selection pressures on wildlife. Phenotypic plasticity is an important mechanism helping organisms establish populations in novel environments. Phenotypic plasticity can be difficult to study in urban wildlife because many urban environmental variables are challenging to isolate and manipulate experimentally. We took advantage of the COVID-19 lockdowns to assess whether urban birds expressed aggression differently when relieved from frequent encounters with humans. We measured the territorial aggression responses of resident dark-eyed juncos (Junco hyemalis) on an urban college campus in Los Angeles, USA. We found that the population overall displayed significantly reduced aggression in pandemic year 2021 compared to the typical year 2019. Furthermore, individuals measured in both 2019 and 2021 showed significantly reduced aggression during 2021, demonstrating that individual birds maintain phenotypic plasticity in this trait. Our results show that human disturbance likely has a significant effect on the aggressive behavior of urban birds.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.12.507677v1" target="_blank">Phenotypic plasticity and the anthropause: an urban bird becomes less aggressive</a>
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<li><strong>Four points regarding reproducibility and external statistical validity: a comment on Walter et al.</strong> -
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Walter et al. (2021) present phase 1–2–3 trial data that show two doses of the BNT162b2 (Pfizer–BioN-Tech) Covid-19 vaccine were safe and effective in children aged 5–11 years. Given that millions of children in this age group are receiving the paediatric Pfizer COVID-19 vaccine, that there are potential risks, and that the balance of benefits over potential risks is more limited in children compared to adults due to low rates of serious disease (ATAGI 2021), gold standards ought to be applied to supporting data in terms of placebo-controlled disease endpoint efficacy trials, safety databases large enough to detect adverse events, and appropriate data sharing to enable reproduction and scrutiny of results. Four points are worthy of attention regarding the reproducibility and external statistical validity of the analysis reported in Walter et al. (2021). ‘External validity’ refers to the extent to which conclusions drawn from the data (and statistical tests thereof) are likely to correspond to, or be generalisable to, the real world (Campbell 1957). ‘Reproducibility’ refers to the ability of independent researchers to draw the same conclusions from the data (Kass et al. 2016).
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🖺 Full Text HTML: <a href="https://osf.io/fswz5/" target="_blank">Four points regarding reproducibility and external statistical validity: a comment on Walter et al.</a>
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<li><strong>The SARS-CoV-2 Spike Protein Mutation Explorer: Using an Interactive Application to Improve the Public Understanding of SARS-CoV-2 Variants of Concern</strong> -
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SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, which began in late 2019 and has resulted in millions of death globally. The need to understand the pandemic means that detailed descriptions of features of this virus are now of interest to non-expert audiences. In particular, there has been much public interest in the spike protein that protrudes from the surface of the SARS-CoV-2 virus particle. The spike is the major determinant of viral infectivity and the main target for protective immune responses, and included in vaccines, and so its properties influence the impact of the pandemic on people’s lives. This protein is rapidly evolving, with mutations that enhance transmissibility or weaken vaccine protection creating new variants of concern (VOCs) and associated sub-lineages. The spread of SARS-CoV-2 VOCs has been tracked by groups such as the COVID-19 Genomics UK consortium (COG-UK). Their online mutation explorer (COG-UK/ME), which analyses and shares SARS-CoV-2 sequence data, contains information about VOCs that is designed primarily for an expert audience but is potentially of general interest during a pandemic. We wished to make this detailed information about SARS-CoV-2 VOCs more widely accessible. Previously work has shown that visualisations and interactivity can facilitate active learning and boost engagement with molecular biology topics, while animations of these topics can boost understanding on protein structure, function, and dynamics. We therefore set out to develop an educational graphical resource, the SARS-CoV-2 Spike Protein Mutation Explorer (SSPME), which contains interactive 3D molecular models and animations explaining SARS-CoV-2 spike protein variants and VOCs. We performed user-testing of the original COG-UK/ME website and of the SSPME, using a within-groups design to measure knowledge acquisition and a between-groups design to contrast the effectiveness and usability. Statistical analysis demonstrated that, when compared to the COG-UK/ME, the SSPME had higher usability and significantly improved participant knowledge confidence and knowledge acquisition. The SSPME therefore provides an example of how 3D interactive visualisations can be used for effective science communication and education on complex biomedical topics, as well as being a resource to improve the public understanding of SARS-CoV-2 VOCs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.09.507349v1" target="_blank">The SARS-CoV-2 Spike Protein Mutation Explorer: Using an Interactive Application to Improve the Public Understanding of SARS-CoV-2 Variants of Concern</a>
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<li><strong>Determinants restricting ACE2 recognition of MERS-related coronaviruses in bats</strong> -
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Phylogenetically distant coronaviruses have evolved to employ ACE2 as their common receptors, including NL63 and many Severe acute respiratory syndrome (SARS) coronavirus-related viruses. Recently, we found two Middle East respiratory syndrome coronaviruses (MERS-CoV)-related bat coronaviruses, NeoCoV and PDF-2180, also use Angiotensin-converting enzyme 2(ACE2) but not MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) for entry. Receptor binding domain (RBD)-binding and pseudovirus entry assays based on a wide range of bat ACE2 orthologs revealed that the two viruses strongly prefer ACE2 from Yangochiropteran bats as compared with Yinpterochiropteran bats, which is not observed in NL63 and SARS-CoV-2. Genetic and structural analyses of the virus-receptor interactions of 50 bat ACE2 orthologs pointed to four crucial host range determinants in two viral binding loops on ACE2. Subsequent functional verifications via mutagenesis on representative ACE2 orthologs confirmed the importance of these determinants on human and bat cells. Remarkably, NeoCoV-T510F, a mutation previously shown to acquire human ACE2 recognition, displayed an expanded potential host range covering most tested bat ACE2, probably due to its reinforced interaction with an evolutionary conserved hydrophobic pocket. Our results elucidated the molecular mechanisms for the species-specific ACE2 usage of MERS-related viruses, offering basic information for assessing the zoonotic risk of these ACE2 utilizing merbecoviruses.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.09.11.507506v1" target="_blank">Determinants restricting ACE2 recognition of MERS-related coronaviruses in bats</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>Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine; Biological: Active Comparator<br/><b>Sponsors</b>: PT Bio Farma; Universitas Padjadjaran; Udayana University<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>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine SCTV01E-1 in Population Aged Above 18 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-1 on D0; Biological: SCTV01E-1 on D28; Biological: SCTV01E-1 on D150; Biological: SCTV01E on D0; Biological: SCTV01E on D28; Biological: SCTV01E on D150; Biological: SCTV01E-1 on D120; Biological: SCTV01E on D120<br/><b>Sponsor</b>: Sinocelltech 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>Efficacy and Safety of ES16001 in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: ES16001 40 mg; Drug: ES16001 80 mg; Drug: ES16001 160 mg; Drug: Placebo<br/><b>Sponsor</b>: Genencell Co. Ltd.<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>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Text Message Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>SCALE-UP Utah II: Community-Academic Partnership to Address COVID-19 Conversational Agent Study</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Text-Messaging (TM); Behavioral: Conversational Agent (CA); Behavioral: Patient Navigation (PN)<br/><b>Sponsors</b>: University of Utah; Utah Department of Health; Association for Utah Community Health; National Institutes of Health (NIH); National Institute on Minority Health and Health Disparities (NIMHD)<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>Multidisciplinary Day-hospital Versus Waiting List Management of Post-COVID-19 Persistent Symptoms (ECHAP-COVID)</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Intervention</b>: Behavioral: Personalized multidisciplinary day-hospital intervention<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<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>Efficacy and Safety Evaluation of Paxlovid for COVID-19: a Real-world Case-control Study</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: standard-of-care plus Paxlovid; Drug: standard-of-care<br/><b>Sponsor</b>: Ruijin Hospital<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>Booster Study of PTX-COVID19-B in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Comirnaty®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>Booster Superiority Study of PTX-COVID19-B Compared to Vaxzevria® in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: PTX-COVID19-B; Biological: Vaxzevria®<br/><b>Sponsor</b>: Everest Medicines (Singapore) Pte. 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>The Impact of a Web-based Psychoeducation Programme With a Motivational AI Chatbot on Covid-19 Vaccine Hesitancy</strong> - <b>Conditions</b>: Vaccine Hesitancy; COVID-19<br/><b>Interventions</b>: Behavioral: AI-driven Vaccine Communicator; Behavioral: Self-learning of COVID-19 vaccine knowledge<br/><b>Sponsor</b>: The Hong Kong Polytechnic University<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>CArdiac REhabilitation for Building Exertional heArt Rate for Chronotropic Incompetence in Long COVID-19</strong> - <b>Conditions</b>: Long COVID; COVID-19<br/><b>Intervention</b>: Behavioral: Cardiac Rehabilitation<br/><b>Sponsor</b>: University of California, San Francisco<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>Rehabilitation Therapy for Post COVID 19 Chronic Fatigue Syndrome</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: intensive combined rehabilitation therapy<br/><b>Sponsor</b>: Cairo University<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>Motivation, Syringe Exchange, and COVID-19</strong> - <b>Condition</b>: COVID-19 Pandemic<br/><b>Intervention</b>: Behavioral: Connect2Test<br/><b>Sponsors</b>: University of Oregon; National Institute on Drug Abuse (NIDA)<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>HRQOL of Life After ECMO Due to COVID-19.</strong> - <b>Conditions</b>: ARDS; COVID-19 Pneumonia; Extracorporeal Membrane Oxygenation<br/><b>Intervention</b>: Other: Phone Interview<br/><b>Sponsor</b>: Medical University of Vienna<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>Phase One Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of MSP008-22 in Healthy Adult Volunteers</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: MSP008-22; Other: Placebo<br/><b>Sponsor</b>: Godavari Biorefineries Limited<br/><b>Not yet recruiting</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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Synthesis, characterization, molecular docking, and anticancer activities of new 1,3,4-oxadiazole-5-fluorocytosine hybrid derivatives</strong> - Analogs of pyrimidine and 1,3,4-oxadiazole are two well established class of molecules proven as potent antiviral and anticancer agents in the pharmaceutical industry. We envisioned designing new molecules where these two heterocycles were conjugated with the goal of enhancing biological activity. In this vein, we synthesized a series of novel pyrimidine-1,3,4-oxadiazole conjugated hybrid molecules as potential anticancer and antiviral agents. Herein, we present a new design for…</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>SARS-CoV-2 main protease (3CL<sup>pro</sup>) interaction with acyclovir antiviral drug/methyl-β-cyclodextrin complex: Physiochemical characterization and molecular docking</strong> - During the current outbreak of the novel coronavirus disease 2019 (COVID-19), researchers have examined several antiviral drugs with the potential to inhibit the proliferation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The antiviral drug acyclovir (AVR), which is used to treat COVID-19, in complex with methyl-β-cyclodextrin (Mβ-CD) was examined in the solution and solid phases. UV-visible and fluorescence spectroscopic analyses confirmed that the guest (AVR) was…</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>DFT and In-silico Investigations along with In-vitro Antitumor and Antimicrobial Assessments of Pharmacological Molecules</strong> - CONCLUSION: The in-silico ADMET studies of the synthesized compounds revealed moderate to good drug likeness, high gastro intestinal (GI) absorption, inhibits the Cytochrome CYP2C19 and CYP2C9 and all the derivatives possess non-cancerous nature. The in-vitro screening demonstrated that several of the novel molecules are promising drug candidates. The density function theory (DFT) theoretical calculations were performed to calculate the energy levels of the FMOs and their energy gabs, dipole…</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 roles of APOBEC-mediated RNA editing in SARS-CoV-2 mutations, replication and fitness</strong> - During COVID-19 pandemic, mutations of SARS-CoV-2 produce new strains that can be more infectious or evade vaccines. Viral RNA mutations can arise from misincorporation by RNA-polymerases and modification by host factors. Analysis of SARS-CoV-2 sequence from patients showed a strong bias toward C-to-U mutation, suggesting a potential mutational role by host APOBEC cytosine deaminases that possess broad anti-viral activity. We report the first experimental evidence demonstrating that APOBEC3A,…</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>Tanshinone IIA loaded bioactive nanoemulsion for alleviation of lipopolysaccharide induced acute lung injury via inhibition of endothelial glycocalyx shedding</strong> - Acute lung injury (ALI) and its more serious form; acute respiratory distress syndrome are major causes of COVID-19 related mortality. Finding new therapeutic targets for ALI is thus of great interest. This work aimed to prepare a biocompatible nanoformulation for effective pulmonary delivery of the herbal drug; tanshinone-IIA (TSIIA) for ALI management. A nanoemulsion (NE) formulation based on bioactive natural ingredients; rhamnolipid biosurfactant and tea-tree oil, was developed using a…</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>ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection</strong> - Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are…</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>Phytochemicals of <em>Cocculus hirsutus</em> deciphered SARS-CoV-2 inhibition by targeting main proteases in molecular docking, simulation, and pharmacological analyses</strong> - The COVID-19 pandemic is spreading rapidly due to the outbreak of novel coronavirus SARS-CoV-2 across the globe. Anti-COVID-19 drugs are urgently required in this situation. In this regard, the discovery of promising new anti-COVID-19 moieties is expected from traditional medicine. The study is aimed to discover phytochemicals of Cocculus hirsutus having anti-COVID-19 activity via inhibiting main proteases of SARS-CoV-2. Main proteases (M^(pro)) of SARS-CoV-2 serve as a protuberant target for…</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>Prostaglandins and non-steroidal anti-inflammatory drugs in Covid-19</strong> - In response to different viral infections, including SARS-CoV-2 infection, pro-inflammatory, anti-inflammatory cytokines, and bioactive lipids are released from infected and immune cells. One of the most critical bioactive lipids is prostaglandins (PGs) which favor perseverance of inflammation leading to chronic inflammation as PGs act as cytokine amplifiers. PGs trigger the release of pro-inflammatory cytokines, activate Th cells, recruit immune cells, and increase the expression of…</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 Natural Products Withaferin A and Withanone from the Medicinal Herb <em>Withania somnifera</em> Are Covalent Inhibitors of the SARS-CoV-2 Main Protease</strong> - The current COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) created a global health crisis. The ability of vaccines to protect immunocompromised individuals and from emerging new strains are major concerns. Hence antiviral drugs against SARS-CoV-2 are essential. The SARS-CoV-2 main protease M^(pro) is vital for replication and an important target for antivirals. Using CMap analysis and docking studies, withaferin A (wifA) and withanone (win), two…</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>Pan-coronavirus fusion inhibitors to combat COVID-19 and other emerging coronavirus infectious diseases</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the currently ongoing COVID-19 pandemic, has posed a serious threat to global public health. Recently, several SARS-CoV-2 variants of concern (VOCs) have emerged and caused numerous cases of reinfection in convalescent COVID-19 patients, as well as breakthrough infections in vaccinated individuals. This calls for the development of broad-spectrum antiviral drugs to combat SARS-CoV-2 and its VOCs. Pan-coronavirus…</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><em>In silico</em> Study Phytosterol <em>Cymbopogon citratus</em> and <em>Curcuma longa</em> as Inhibitor Agent 3C-Like Protease SARS-CoV-2</strong> - <b>Background and Objective:</b> Lemongrass (<i>Cymbopogon citratus</i>) and turmeric (<i>Curcuma longa</i>) are widely used by the community for traditional medicinal spices and cooking spices. In the era of the COVID-19 pandemic, people use lemongrass and turmeric to increase immunity and protect the body from infection with the SARS-CoV-2 virus. However, the antiviral mechanisms have not been studied much. This study aims to predict the bioactivity of the…</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 diamine fluoride therapy for dental care</strong> - Silver diamine fluoride (SDF) was developed in Japan in the 1960s. It is used to control early childhood caries, arrest root caries, prevent fissure caries and secondary caries, desensitise hypersensitive teeth, remineralise hypomineralised teeth, prevent dental erosion, detect carious tissue during excavation and manage infected root canals. SDF is commonly available as a 38% solution containing 255,000 ppm silver and 44,800 ppm fluoride ions. Silver is an antimicrobial and inhibits cariogenic…</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>Vandetanib Blocks the Cytokine Storm in SARS-CoV-2-Infected Mice</strong> - The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib, paxlovid, and molnupiravir), or in advanced clinical trials. Vandetanib is a kinase inhibitor which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), as well as the RET-tyrosine kinase. In the current study, it was tested in different cell lines and showed promising…</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>Elucidating the enhanced binding affinity of a double mutant SP-D with trimannose on the influenza A virus using molecular dynamics</strong> - Surfactant protein D (SP-D) is an essential component of the human pulmonary surfactant system, which is crucial in the innate immune response against glycan-containing pathogens, including Influenza A viruses (IAV) and SARS-CoV-2. Previous studies have shown that wild-type (WT) SP-D can bind IAV but exhibits poor antiviral activities. However, a double mutant (DM) SP-D consisting of two point mutations (Asp325Ala and Arg343Val) inhibits IAV more potently. Presently, the structural mechanisms…</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>Degradation of Chloroquine Phosphate by UV-activated Persulfate</strong> - The degradation of chloroquine phosphate (CQP), an anti-COVID-19 drug, was investigated in a UV-activated persulfate system (UV/PS). The second-order rate constants of CQP with hydroxyl radicals (HO·) and sulfate radicals (SO(4)^(-)·) were determined using a competition kinetics experiment, and the effects of persulfate concentration, pH, and inorganic anions on the degradation of CQP were also systematically studied. Furthermore, a kinetic model was established to predict the concentration of…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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