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180 lines
56 KiB
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<title>15 August, 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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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<ul>
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<li><strong>Revisiting the small-world property of co-enrollment networks: A network analysis of hybrid course delivery strategies</strong> -
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<div>
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Infectious disease outbreaks bring new challenges to campus operations at institutions of higher education (IHEs). At the beginning of the COVID-19 pandemic, as a precaution against COVID-19 transmission on their campuses, many IHEs shifted to entirely remote courses in the Spring 2020 semester. As these institutions prepared for the Fall 2020 semester, their administrations evaluated the extent to which remote courses should continue. While remote courses may reduce the number of students who interact on campus and thus mitigate the risk of disease spread, there may be academic and financial downsides. Methodology: With de-identified enrollment, course schedule, and student profile data from the Fall 2019 semester at Georgia Institute of Technology (Georgia Tech), we construct a co-enrollment network, which is a representation of student connections through courses. In this co-enrollment network, we observe the small-world property in which the average path length among reachable student pairs is short and nearly all students are connected to each other in the main component of the network through multiple independent paths. We also see high connectivity between different majors. Then, we apply various hybrid instructional mode strategies to this co-enrollment network and use network connectivity and in-person instruction metrics to compare these strategies from both health and academic perspectives, by their impacts on various groups of students, and based on the trade-off between network connectivity and in-person instruction. Results: Although these strategies result in decreased network connectivity, they do not remove the small-world property. When comparing the strategies in terms of network connectivity, we find three different strategy types to be the most favorable. Even under these strategies, the percentage of students with in-person courses that could be exposed rises quickly with initial infection rates. When comparing the strategies in terms of in-person instruction, the most favorable strategies select a fixed percentage of courses for each subject to be delivered remotely. We then consider the impacts of these strategies on various groups of students to evaluate if there may be disparate impacts across these groups. In general, we find that strategies with more remote courses result in less disparate impacts on network connectivity and in-person instruction across these groups. In addition, we generally see less in-person instruction for lower-level students (i.e. first-year students and sophomores) compared to upper-level students. Regarding the trade-off between network connectivity and in-person instruction, the only strategy that is suboptimal under all scenarios in this study is the 1000s and 4000s only strategy, which keeps all 1000- and 4000-level courses in-person. This is because of its large quantity of remote courses, the large 1000- and 4000- level courses, the highly central 1000- level courses, and the high connectivity among first-year students and seniors. Importance: By quantitatively comparing network connectivity and in-person instruction for these various strategies, campus administrators can weigh the physical health, academic performance, and mental health of students, along with the financial well-being of their academic institution when responding to infectious disease outbreaks.
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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://osf.io/jp6aq/" target="_blank">Revisiting the small-world property of co-enrollment networks: A network analysis of hybrid course delivery strategies</a>
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</div></li>
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<li><strong>SARS-CoV-2 Neutralizing Antibodies Following a Second BA.5 Bivalent Booster</strong> -
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<div>
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Bivalent COVID-19 mRNA vaccines expressing both the ancestral D614G and Omicron BA.5 spike proteins were introduced in August 2022 with the goal of broadening immunity to emerging SARS-CoV-2 Omicron subvariants. Subsequent studies on bivalent boosters found neutralizing antibody responses similar to boosters with the original monovalent vaccine, likely the result of immunological imprinting. Guidelines allow for administration of a second bivalent booster in high-risk groups, but it remains unknown whether this would broaden antibody responses. To address this question, we assessed longitudinal serum SARS-CoV-2-neutralizing titers in 18 elderly immunocompetent individuals (mean age 69) following a fourth monovalent booster and two BA.5 bivalent booster vaccines using pseudovirus neutralization assays against D614G, Omicron BA.5, and Omicron XBB.1.5. There was a small but significant increase in peak neutralizing antibody responses against Omicron BA.5 and XBB.1.5 following the first bivalent booster, but no significant increase in peak titers following the second bivalent booster. Omicron-specific neutralizing titers remained low after both doses of the BA.5 bivalent booster. Our results suggest that a second dose of the BA.5 bivalent booster is not sufficient to broaden antibody responses and to overcome immunological imprinting. A monovalent vaccine targeting only the spike of the recently dominant SARS-CoV-2 may mitigate the back boosting associated with the original antigenic sin.
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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.biorxiv.org/content/10.1101/2023.08.13.553148v1" target="_blank">SARS-CoV-2 Neutralizing Antibodies Following a Second BA.5 Bivalent Booster</a>
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</div></li>
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<li><strong>Impact of age and sex on neuroinflammation following SARS-CoV-2 infection in a murine model</strong> -
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<div>
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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for the worldwide COVID-19 pandemic, is known to infect people of all ages and both sexes. Senior populations have the greatest risk of severe disease, and sexual dimorphism in clinical outcomes has been reported in COVID-19. SARS-CoV-2 infection in humans can cause damage to multiple organ systems, including the brain. Neurological symptoms are widely observed in patients with COVID-19, with many survivors suffering from persistent neurological and cognitive impairment, potentially accelerating Alzheimer's disease. The present study aims to investigate the impact of age and sex on the neuroinflammatory response to SARS-CoV-2 infection using a mouse model. Wild-type C57BL/6 mice were inoculated, by intranasal route, with SARS-CoV-2 lineage B.1.351 variant known to infect mice. Older animals and in particular males exhibited a significantly greater weight loss starting at 4 dpi. In addition, male animals exhibited higher viral RNA loads and higher titers of infectious virus in the lung, which was particularly evident in males at 16 months of age. Notably, no viral RNA was detected in the brains of infected mice, regardless of age or sex. Nevertheless, expression of IL-6, TNF-, and CCL-2 in the lung and brain was increased with viral infection. An unbiased brain RNA-seq/transcriptomic analysis showed that SARS-CoV-2 infection caused significant changes in gene expression profiles in the brain, with innate immunity, defense response to virus, cerebravascular and neuronal functions, as the major molecular networks affected. The data presented in this study show that SARS-CoV-2 infection triggers a neuroinflammatory response despite the lack of detectable virus in the brain. Age and sex have a modifying effect on this pathogenic process. Aberrant activation of innate immune response, disruption of blood-brain barrier and endothelial cell integrity, and supression of neuronal activity and axonogenesis underlie the impact of SARS-CoV-2 infection on the brain. Understanding the role of these affected pathways in SARS-CoV-2 pathogenesis helps identify appropriate points of therapeutic interventions to alleviate neurological dysfunction observed during COVID-19.
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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.biorxiv.org/content/10.1101/2023.08.11.552998v1" target="_blank">Impact of age and sex on neuroinflammation following SARS-CoV-2 infection in a murine model</a>
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</div></li>
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<li><strong>Pandemic preparedness through genomic surveillance: Overview of mutations in SARS-CoV-2 over the course of COVID-19 outbreak</strong> -
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<div>
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Genomic surveillance is a vital strategy for preparedness against the spread of infectious diseases and to aid in development of new treatments. In an unprecedented effort, millions of samples from COVID-19 patients have been sequenced worldwide for SARS-CoV-2. Using more than 8 million sequences that are currently available in GenBank SARS-CoV-2 database, we report a comprehensive overview of mutations in all 26 proteins and open reading frames (ORFs) from the virus. The results indicate that the spike protein, NSP6, nucleocapsid protein, envelope protein and ORF7b have shown the highest mutational propensities so far (in that order). In particular, the spike protein has shown rapid acceleration in mutations in the post-vaccination period. Monitoring the rate of non-synonymous mutations (Ka) provides a fairly reliable signal for genomic surveillance, successfully predicting surges in 2022. Further, the external proteins (spike, membrane, envelope, and nucleocapsid proteins) show a significant number of mutations compared to the NSPs. Interestingly, these four proteins showed significant changes in Ka typically 2 to 4 weeks before the increase in number of human infections (surges). Therefore, our analysis provides real time surveillance of mutations of SARS-CoV-2, accessible through the project website http://pandemics.okstate.edu/covid19/. Based on ongoing mutation trends of the virus, predictions of what proteins are likely to mutate next are also made possible by our approach. The proposed framework is general and is thus applicable to other pathogens. The approach is fully automated and provides the needed genomic surveillance to address a fast-moving pandemic such as COVID-19.
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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.biorxiv.org/content/10.1101/2023.08.12.553079v1" target="_blank">Pandemic preparedness through genomic surveillance: Overview of mutations in SARS-CoV-2 over the course of COVID-19 outbreak</a>
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</div></li>
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<li><strong>Met58 and di-acidic motif located at C-terminal region of SARS-CoV-2 ORF6 plays a crucial role in its structural conformations</strong> -
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<div>
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Despite being mostly neglected in structural biology, the C-terminal Regions (CTRs) are studied to be multifunctional in humans as well as in viruses. Their role in cellular processes such as trafficking, protein-protein interactions, and protein-lipid interactions are known due to their structural properties. In our previous findings on SARS-CoV-2 Spike and NSP1 proteins, the C-terminal regions (CTRs) are observed to be disordered and experimental evidence showed a gain of structure properties in different physiological environments. In this line, we have investigated the structural dynamics of CTR (residues 38-61) of SARS-CoV-2 ORF6 protein, disrupting bidirectional transport between the nucleus and cytoplasm. Like Spike and NSP1-CTR, the ORF6-CTR is also disordered in nature but possesses gain of structure properties in minimal physiological conditions. As per studies, the residue such as Methionine at 58th position in ORF6 is critical for interaction with Rae1-Nup98. Therefore, along with M58, we have identified a few other mutations from the literature and performed extensive structure modelling and dynamics studies using computational simulations. The exciting revelations in CTR models provide evidence of its structural flexibility and possible capabilities to perform multifunctionality inside the host.
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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.biorxiv.org/content/10.1101/2023.08.14.553212v1" target="_blank">Met58 and di-acidic motif located at C-terminal region of SARS-CoV-2 ORF6 plays a crucial role in its structural conformations</a>
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</div></li>
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<li><strong>Transmission bottleneck size estimation from de novo viral genetic variation</strong> -
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<div>
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Sequencing of viral infections has become increasingly common over the last decade. Deep sequencing data in particular have proven useful in characterizing the roles that genetic drift and natural selection play in shaping within-host viral populations. They have also been used to estimate transmission bottleneck sizes from identified donor-recipient pairs. These bottleneck sizes quantify the number of viral particles that establish genetic lineages in the recipient host and are important to estimate due to their impact on viral evolution. Current approaches for estimating bottleneck sizes exclusively consider the subset of viral sites that are observed as polymorphic in the donor individual. However, allele frequencies can change dramatically over the course of an individual's infection, such that sites that are polymorphic in the donor at the time of transmission may not be polymorphic in the donor at the time of sampling and allele frequencies at donor-polymorphic sites may change dramatically over the course of a recipient's infection. Because of this, transmission bottleneck sizes estimated using allele frequencies observed at a donor's polymorphic sites may be considerable underestimates of true bottleneck sizes. Here, we present a new statistical approach for instead estimating bottleneck sizes using patterns of viral genetic variation that arose de novo within a recipient individual. Specifically, our approach makes use of the number of clonal viral variants observed in a transmission pair, defined as the number of viral sites that are monomorphic in both the donor and the recipient but carry different alleles. We first test our approach on a simulated dataset and then apply it to both influenza A virus sequence data and SARS-CoV-2 sequence data from identified transmission pairs. Our results confirm the existence of extremely tight transmission bottlenecks for these two respiratory viruses, using an approach that does not tend to underestimate transmission bottleneck sizes.
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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.biorxiv.org/content/10.1101/2023.08.14.553219v1" target="_blank">Transmission bottleneck size estimation from de novo viral genetic variation</a>
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</div></li>
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<li><strong>Mutational basis of serum cross-neutralization profiles elicited by infection or vaccination with SARS-CoV-2 variants</strong> -
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<div>
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A series of SARS-CoV-2 variants emerged during the pandemic under selection for neutralization resistance. Convalescent and vaccinated sera show consistently different cross-neutralization profiles depending on infecting or vaccine variants. To understand the basis of this heterogeneity, we modeled serum cross-neutralization titers for 165 sera after infection or vaccination with historically prominent lineages tested against 18 variant pseudoviruses. Cross-neutralization profiles were well captured by models incorporating autologous neutralizing titers and combinations of specific shared and differing mutations between the infecting/vaccine variants and pseudoviruses. Infecting/vaccine variant-specific models identified mutations that significantly impacted cross-neutralization and quantified their relative contributions. Unified models that explained cross-neutralization profiles across all infecting and vaccine variants provided accurate predictions of holdout neutralization data comprising untested variants as infecting or vaccine variants, and as test pseudoviruses. Finally, comparative modeling of 2-dose versus 3-dose mRNA-1273 vaccine data revealed that the third dose overcame key resistance mutations to improve neutralization breadth.
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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/10.1101/2023.08.13.553144v1" target="_blank">Mutational basis of serum cross-neutralization profiles elicited by infection or vaccination with SARS-CoV-2 variants</a>
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<li><strong>Structural elucidation and antiviral activity of cathepsin L inhibitors with carbonyl and epoxide warheads</strong> -
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<div>
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Emerging RNA viruses including SARS-CoV-2 continue to be a major threat around the globe. The cell entry of SARS-CoV-2 particles via the endosomal pathway involves the cysteine protease cathepsin L (CatL) among other proteases. CatL is rendered as a promising drug target in the context of different viral and lysosome-related diseases. Hence, drug discovery and structure-based optimization of inhibitors is of high pharmaceutical interest. We herein verified and compared the anti-SARS-CoV-2 activity of a set of carbonyl and succinyl-epoxide-based inhibitors, which have previously been identified as cathepsin inhibitors. Calpain inhibitor XII (CI-XII), MG-101 and CatL inhibitor IV (CLI-IV) possess antiviral activity in the very low nanomolar IC50 range in Vero E6 cells. Experimental structural data on how these and related compounds bind to CatL are however notably lacking, despite their therapeutic potential. Consequently, we present and compare crystal structures of CatL in complex with 14 compounds, namely BOCA (N-BOC-2-aminoacetaldehyde), CLI-IV, CI-III, CI-VI, CI-XII, the main protease alpha-ketoamide inhibitor 13b, MG-101, MG-132 as well as E-64d (aloxistatin), E-64, CLIK148, CAA0225, TC-I (CID 16725315) and TPCK at resolutions better than 2 Angstrom. Overall, the presented data comprise a broad and solid basis for structure-guided understanding and optimization of CatL inhibitors towards protease drug development.
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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.biorxiv.org/content/10.1101/2023.08.11.552671v1" target="_blank">Structural elucidation and antiviral activity of cathepsin L inhibitors with carbonyl and epoxide warheads</a>
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</div></li>
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<li><strong>PRIEST - Predicting viral mutations with immune escape capability of SARS-CoV-2 using temporal evolutionary information</strong> -
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<div>
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The dynamic evolution of the SARS-CoV-2 virus is largely driven by mutations in its genetic sequence, culminating in the emergence of variants with increased capability to evade host immune responses. Accurate prediction of such mutations is fundamental in mitigating pandemic spread and developing effective control measures. In this study, we introduce a robust and interpretable deep-learning approach called PRIEST. This innovative model leverages time-series viral sequences to foresee potential viral mutations. Our comprehensive experimental evaluations underscore PRIEST's proficiency in accurately predicting immune-evading mutations. Our work represents a substantial step forward in the utilization of deep-learning methodologies for anticipatory viral mutation analysis and pandemic response.
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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/10.1101/2023.08.11.552988v1" target="_blank">PRIEST - Predicting viral mutations with immune escape capability of SARS-CoV-2 using temporal evolutionary information</a>
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</div></li>
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<li><strong>Lactobacillus rhamnosus (LR) ameliorates acute respiratory distress syndrome (ARDS) via modulating the lung Innate Lymphoid Cells (ILCs)-Mononuclear Phagocytic System (MPS)</strong> -
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<div>
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Acute-respiratory-distress-syndrome (ARDS), the ultimate manifestation of acute-lung-injury (ALI) is a life-threatening respiratory failure with a significantly higher incidence and mortality worldwide. Recent discoveries have emphasized the existence of a potential nexus between gut and lung-health wherein physiology of the gut is directly linked with the outcomes of the lung pathologies. These discoveries fuel novel approaches including probiotics for the treatment of several respiratory disorders including ALI/ARDS. Lactobacillus rhamnosus (LR) is a preferred probiotic of choice as it has been reported to exhibit potent anti-inflammatory activities in various inflammatory diseases. In the present study, we investigated the prophylactic-potential of LR in lipopolysaccharide (LPS)-induced ALI/ARDS mice model, which mimics the pathophysiology of several respiratory disorders including respiratory tract infections, COVID-19, influenza, pneumonia, asthma, tuberculosis, cystic fibrosis, chronic obstructive pulmonary disease (COPD) etc. Our in vivo findings revealed that pretreatment with LR significantly attenuated lung inflammation and improved the pathophysiology of lung-tissues in ALI/ARDS mice. We observed that LR-administration suppressed the LPS-induced inflammatory cell infiltration in the lungs via ameliorating vascular-permeability (edema) of the lungs. Acute and chronic lung-disorders, including ARDS, are largely governed by innate-immune response. Interestingly, we observed that LR via modulating different ILCs (first responder to infections) subsets viz. ILC1, ILC2 and ILC3 prevent lung-fibrosis and maintain vascular permeability in LPS induced ALI/ARDS mice model. Of note, we observed a significant-enhancement in the percentage of inflammatory IL-17 producing CD3-Roryt+NKp46- ILC3-fraction along with a significant reduction in IL-22 (responsible for vascular integrity) producing CD3-Roryt+NKp46+ ILC3 in both the BALF and lung-tissues. These ILCs would further augment the activation and recruitment of mononuclear phagocytic system (MPS-monocytes, macrophages and DCs) along with neutrophils and eosinophils in the lungs and BALF in ALI/ARDS mice model. Furthermore, gene expression and protein-analysis demonstrated that LR treatment significantly reduces the expression of inflammatory-cytokines in lung tissue and serum, thereby suggesting its potent immunomodulatory activity in attenuating ALI/ARDS. Summarily, our research convincingly establishes the prophylactic-role of LR in the prevention and management of respiratory-distress syndromes driven by the diverse inflammatory insults via modulating the lungs ILCs-MPS axis with significant clinical-implications for the management of COVID-19, Influenza, COPD etc.
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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/10.1101/2023.08.10.552899v1" target="_blank">Lactobacillus rhamnosus (LR) ameliorates acute respiratory distress syndrome (ARDS) via modulating the lung Innate Lymphoid Cells (ILCs)-Mononuclear Phagocytic System (MPS)</a>
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<li><strong>Subphenotypes of Self-Reported Symptoms and Outcomes in Long COVID: a prospective cohort study with latent class analysis.</strong> -
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Objective: To characterize subphenotypes of self-reported symptoms and outcomes(SRSOs) in Post-acute sequelae of COVID-19(PASC). Design: Prospective, observational cohort study of PASC subjects. Setting: Academic tertiary center from five clinical referral sources. Participants: Adults with COVID-19 ≥ 20 days before enrollment and presence of any new self-reported symptoms following COVID-19. Exposures: We collected data on clinical variables and SRSOs via structured telephone interviews and performed standardized assessments with validated clinical numerical scales to capture psychological symptoms, neurocognitive functioning, and cardiopulmonary function. We collected saliva and stool samples for quantification of SARS-CoV-2 RNA via qPCR. Primary and Secondary outcomes of measure: Description of PASC SRSOs burden and duration, derivation of distinct PASC subphenotypes via latent class analysis (LCA), and relationship between viral load with SRSOs and PASC subphenotypes. Results: Baseline data for 214 individuals were analyzed. The study visit took place at a median of 197.5 days after COVID-19 diagnosis, and participants reported ever having a median of 9/16 symptoms (interquartile range 6-11) after acute COVID, with muscle-aches, dyspnea, and headache being the most common. Fatigue, cognitive impairment, and dyspnea were experienced for a longer time. Participants had a lower burden of active symptoms (median 3, interquartile range 1-6) than those ever experienced (p<0.001). Unsupervised LCA of symptoms revealed three clinically-active PASC subphenotypes: a high burden constitutional symptoms (21.9%) , a persistent loss/change of smell and taste (20.6%) , and a minimal residual symptoms subphenotype (57.5%). Subphenotype assignments were strongly associated with self-assessments of global health, recovery and PASC impact on employment (p<0.001). Viral persistence (5.6% saliva and 1% stool samples positive) did not explain SRSOs or subphenotypes. Conclusions: We identified distinct PASC subphenotypes and highlight that although most symptoms progressively resolve, specific PASC subpopulations are impacted by either high burden of constitutional symptoms or persistent olfactory/gustatory dysfunction, requiring prospective identification and targeted preventive or therapeutic interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.09.23293901v1" target="_blank">Subphenotypes of Self-Reported Symptoms and Outcomes in Long COVID: a prospective cohort study with latent class analysis.</a>
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<li><strong>Analysis of SARS-CoV-2 Variant-Specific Serum Antibodies Post-Vaccination Utilizing Immortalized Human Hepatocyte-like Cells (HLC) to Assess Development of Protective Immunity</strong> -
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Abstract Background: Our previous studies demonstrated that SARS-CoV-2 spike proteins could bind to hepatocytes via the asialoglycoprotein receptor-1 (ASGR-1) facilitating direct infection by the SARS-CoV-2 virus. Immortalized E12-HLC expressed the phenotypic and biological properties of primary human hepatocytes, including their ability to bind spike proteins via ASGR-1 with exception of the spike 1 protein. This binding could be inhibited by spike protein-specific monoclonal antibodies. We used the same spike-blocking analysis to determine if post-vaccination serum was capable of blocking spike protein binding to HLC. Samples collected from subjects prior to, and post-vaccination were quantified for anti-variant-specific antibody (original wild type, alpha (α), beta (β), gamma (γ), and delta (δ) variants by a flow cytometry based immunofluorescent assay. Inhibition of variant spike protein binding to HLC and AT-2 (as a known model for spike 1 binding to the ACE-2 receptor) was analyzed by confocal microscopy. This study was designed to investigate the ability of post-vaccination antibodies to mediate immunity to spike S2, and to validate the utility of the E12-HLC in analyzing that immunity. Methods: Serum was collected from 10 individuals pre- and post-vaccination with the J&J, Moderna or Pfizer vaccines. The serum samples were quantified for variant-specific antibodies in a flow cytometry-based immunofluorescent assay utilizing beads coated with biotinylated variant spike proteins (α, β, γ, δ).Presence of variant-specific antibodies was visualized by anti-human IgG-Alexa 488. Inhibition of spike protein binding to cells was analyzed by immunofluorescent confocal analysis. Biotinylated variant spike proteins were preincubated with serum samples and then tested for binding to target cells. Binding was visualized by Streptavidin-Alexa 594. Results were compared to binding of unblocked spike variants. Results: All variant spike proteins tested bound to both the HLC and AT-2 cells. Pre-vaccination serum samples had no detectable reactivity to any of the variant spike proteins and were unable to inhibit binding of the variant spike proteins to either target cell. Post-vaccination serum samples demonstrated a progression of SARS-CoV-2 antibody levels from low early post-vaccination levels to higher levels at 2.5 months after vaccination. Concurrently, serum samples taken at those different timeframes demonstrated that serum obtained from shortly after vaccination were not as effective in blocking spike protein as serum obtained after 2.5 months post-vaccination. Antibody concentrations were not necessarily associated with better blocking of spike protein binding as spike variant-specific serum antibody concentrations varied significantly between subjects and within each subject. It was also demonstrated that vaccination with all the various available vaccines stimulated antibodies that inhibited binding of the available variant spike proteins to both HLC and AT-2 cells. Conclusion: HLC, along with AT-2 cells, provides a useful platform to study the development of protective antibodies that prevent the binding SARS-CoV-2 spike proteins to target cells. It was shown that vaccination with the three available vaccines all elicited serum antibodies that were protective against binding of each of the variant spike proteins to both AT-2 and HLC cells. This study suggests that analysis of immune serum to block spike binding to target cells may be a more useful technique to assess protective immunity than quantitation of gross antibody alone.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.08.23293863v1" target="_blank">Analysis of SARS-CoV-2 Variant-Specific Serum Antibodies Post-Vaccination Utilizing Immortalized Human Hepatocyte-like Cells (HLC) to Assess Development of Protective Immunity</a>
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<li><strong>Immunogenicity of mRNA-1273 and BNT162b2 in Immunocompromised Patients: Systematic Review and Meta-Analysis Using GRADE</strong> -
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Aim: Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose COVID-19 vaccines may offer increased immunogenicity. Materials & methods: A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. Results: mRNA-1273 was associated with a significantly higher seroconversion likelihood (relative risk, 1.11 [95% CI, 1.08, 1.14]; P<0.0001; I2=66.8%) and higher total antibody titers (relative increase, 50.45% [95% CI, 34.63%, 66.28%]; P<0.0001; I2=89.5%) versus BNT162b2. mRNA-1273 elicited higher but statistically nonsignificant relative increases in neutralizing antibody titers and cellular immune responses versus BNT162b2. Conclusion: Higher-dose mRNA-1273 had increased immunogenicity versus BNT162b2 in IC patients.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.09.23293898v1" target="_blank">Immunogenicity of mRNA-1273 and BNT162b2 in Immunocompromised Patients: Systematic Review and Meta-Analysis Using GRADE</a>
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<li><strong>A community based cross-sectional study on impact assessment of COVID-19 on mental health in Central India</strong> -
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The current study is a cross-sectional survey that aims to assess the effect of COVID-19 on mental health in rural India. The study was conducted in the Durg district of Chhattisgarh state, and it used the Generalized Anxiety Disorder Assessment (GAD-7), PHQ-9, and IES-R to evaluate the prevalence of depression, anxiety, and PTSD among the community. Out of 431 participants, 44% were male, with a mean age of 41 years. The study found that 87% of the participants had health insurance, 40% had co-morbidities like hypertension or diabetes, and half of them experienced food shortage and change in income during the pandemic. One-third of the participants experienced death among one or more family members due to the pandemic. The study found that the mean scores of IES-R, GAD-7, and PHQ-9 were 23.59-24.91, 1.50, 2.07, and 1.06-1.58, respectively. Thirty percent of the participants observed some distress, 15% reported depression, and 12% reported anxiety. The adjusted effect of death in the family due to COVID-19 was found to be significantly associated with higher risk of mental distress, whereas education was associated with lower risk of distress. Depression and anxiety were more common among the elderly and less common among individuals living in nuclear families. Scarcity of food and change in income were significantly associated with anxiety. These findings highlight the need for increased support for mental health in rural communities in India, particularly in the face of the COVID-19 pandemic.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.08.08.23293808v1" target="_blank">A community based cross-sectional study on impact assessment of COVID-19 on mental health in Central India</a>
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<li><strong>To what extent are Chinese international students in Leuven influenced by the educational thoughts of Confucius when coping with the Covid-19 pandemic situation?</strong> -
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The Chinese education market is the largest in Higher Education (HE) worldwide. The number of study-abroad Chinese students has experienced a constant growth throughout the previous decade. According to the Chinese Ministry of Education report, there were more than 660,000 Chinese students studying in different countries in 2018. This demonstrates the growing desire from Chinese students, as well as their parents, to integrate in multicultural contexts in order to broaden horizons in this modern era (Gao, 2018). However, recent studies revealed that Chinese overseas students have less affinity to different cultures and face many difficulties in integrating with students of different cultural backgrounds (Yu and Moskal, 2018). Both internal and external culture differences are the key factors behind Chinese students lacking ability for intercultural integration (Zhu and Gao, 2012), which is also associated with their difficulty in adapting in a different education system. Chinese overseas students come from a Confucian Heritage Culture where Confucianism has shaped the culture that has been deeply rooted in the Chinese education system. This has formed the students’ mind-set, resulting in certain personality traits related to social communication. Modesty, social and ritual propriety are the main tenets of Confucian traditionalism. It has become the standard for Chinese peoples’ social and moral behaviours, gives order to and strengthens the social connections between people. This mind-set influences Chinese international students’ cross-cultural communication, both in multilingual and multicultural contexts (Luo, Huang and Najjar, 2007). Taking the Covid-19 pandemic into consideration, it was observed that Chinese overseas students in different countries have proactively taken medical solutions for self-prevention in the crisis situation. In order to identify the role of Confucian Heritage Cultures influence in Chinese international students adapting to overseas education environments, this study examines the previous work on Confucian Heritage Culture involvement in Chinese education. It is designed to measure, to what extent are Chinese international students in Leuven influenced by Confucian Heritage Culture when coping with the Covid-19 pandemic situation during overseas study. The conducted thesis includes an academic review on Confucian Heritage Culture as a fundamental cultural factor in Chinese education system, a qualitative study and an analysis of Chinese international students in Leuven experience Confucian Heritage Culture to cope with lockdown situations. This thesis aims to explore the possible revelation of acculturation competence among Chinese international students within the coronavirus pandemic background.
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🖺 Full Text HTML: <a href="https://osf.io/q2afv/" target="_blank">To what extent are Chinese international students in Leuven influenced by the educational thoughts of Confucius when coping with the Covid-19 pandemic situation?</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>A Study to Evaluate the Safety and Immunogenicity of an (Omicron Subvariant) COVID-19 Vaccine Booster Dose in Previously Vaccinated Participants and Unvaccinated Participants.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: XBB.1.5 Vaccine (Booster); Biological: XBB.1.5 Vaccine (single dose)<br/><b>Sponsor</b>: Novavax<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>Effect of Natural Food on Gut Microbiome and Phospholipid Spectrum of Immune Cells in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: Freeze-dried Mare Milk (Saumal)<br/><b>Sponsor</b>: Asfendiyarov Kazakh National Medical 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>EFFECT OF COGNITIVE BEHAVIORAL THERAPY ON DEPRESSION AND QUALITY OF LIFE IN PATIENTS WITH POST COVID-19</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Behavioral: rehacom<br/><b>Sponsor</b>: Cairo University<br/><b>Enrolling by invitation</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>Intradermal Administration of a COVID-19 mRNA Vaccine in Elderly</strong> - <b>Conditions</b>: Vaccination; Infection; COVID-19<br/><b>Intervention</b>: Biological: Comirnaty<br/><b>Sponsor</b>: Radboud University Medical Center<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 Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: mRNA-CR-04 vaccine 10μg; Biological: mRNA-CR-04 vaccine 30μg; Biological: mRNA-CR-04 vaccine 100μg; Drug: Placebo<br/><b>Sponsor</b>: GlaxoSmithKline<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>Methylprednisolone in Patients With Cognitive Deficits in Post-COVID-19 Syndrome (PCS)</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Drug: Methylprednisolone<br/><b>Sponsor</b>: Charite University, Berlin, Germany<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>Phase 3 Adolescent Study for SARS-CoV-2 rS Variant Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2601 co-formulated Omicron XBB.1.5 SARS-CoV-2 rS vaccine; Biological: Prototype/XBB.1.5 Bivalent Vaccine (5 µg)<br/><b>Sponsor</b>: Novavax<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>Hyperbaric on Pulmonary Functions in Post Covid -19 Patients.</strong> - <b>Condition</b>: Post COVID-19 Patients<br/><b>Interventions</b>: Device: hyperbaric oxygen therapy; Device: breathing exercise; Drug: medical treatment<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>Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Fatigue<br/><b>Interventions</b>: Other: Dietary intervention to mitigate Post-Acute COVID-19 Syndrome; Other: Attention Control<br/><b>Sponsor</b>: University of Maryland, Baltimore<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 Phase II Trial to Evaluate the Safety and Immunogenicity of BIMERVAX® When Coadministered With Seasonal Influenza Vaccine (SIIV) in Adults Older Than 65 Years of Age Fully Vaccinated Against COVID-19</strong> - <b>Conditions</b>: SARS CoV 2 Infection; Influenza, Human<br/><b>Interventions</b>: Biological: BIMERVAX; Biological: SIIV<br/><b>Sponsor</b>: Hipra Scientific, S.L.U<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>Directed Topical Drug Delivery for Treatment for PASC Hyposmia</strong> - <b>Condition</b>: Post Acute Sequelae Covid-19 Hyposmia<br/><b>Interventions</b>: Drug: Beclomethasone; Other: Placebo; Device: Microsponge<br/><b>Sponsor</b>: Duke 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>Preliminary Efficacy of a Technology-based Physical Activity Intervention for Older Korean Adults During the COVID-19 Pandemic</strong> - <b>Conditions</b>: Cardiovascular Health; Physical Function<br/><b>Intervention</b>: Behavioral: Golden Circle<br/><b>Sponsor</b>: University of Illinois at Urbana-Champaign<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>Supported Employment COVID-19 Rapid Testing for PWID</strong> - <b>Condition</b>: Health Behavior<br/><b>Intervention</b>: Behavioral: Supported Employment<br/><b>Sponsor</b>: University of Oregon<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>Telerehabilitation for Post COVID-19 Condition</strong> - <b>Conditions</b>: Long COVID; Chronic Fatigue Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program based on cardiorespiratory principles<br/><b>Sponsors</b>: Université de Sherbrooke; Hotel Dieu Hospital<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>Study of Tixagevimab/Cilgavimab and Regdanvimab Efficacy for Treatment of COVID-19</strong> - <b>Condition</b>: Coronavirus Infections<br/><b>Interventions</b>: Drug: tixagevimab/cilgavimab 150+150 mg; Drug: tixagevimab/cilgavimab 300+300 mg; Drug: regdanvimab<br/><b>Sponsors</b>: City Clinical Hospital No.52 of Moscow Healthcare Department; Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation<br/><b>Active, not recruiting</b></p></li>
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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>Identification of Promising Sulfonamide Chalcones as Inhibitors of SARS-CoV-2 3CL<sup>pro</sup> through Structure-Based Virtual Screening and Experimental Approaches</strong> - 3CL^(pro) is a viable target for developing antiviral therapies against the coronavirus. With the urgent need to find new possible inhibitors, a structure-based virtual screening approach was developed. This study recognized 75 pharmacologically bioactive compounds from our in-house library of 1052 natural product-based compounds that satisfied drug-likeness criteria and exhibited good bioavailability and membrane permeability. Among these compounds, three promising sulfonamide chalcones were…</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>TGF-β1 inhibition of ACE2 mediated by miRNA uncovers novel mechanism of SARS-CoV-2 pathogenesis</strong> - SARS-CoV-2 utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin-converting enzyme 2 (ACE2). Decreased cell surface density of ACE2 contributes to mortality during COVID-19. Studies published early during the pandemic reported that people with cystic fibrosis (PwCF) treated with the high efficiency CFTR modulators ETI (elexacaftor-tezacaftor-ivacaftor) had higher ACE2 levels and milder COVID-19 symptoms, compared to people without CF. Subsequent studies did…</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>Endogenous and Therapeutic 25-hydroxycholesterols May Worsen Early SARS-CoV-2 Pathogenesis in Mice</strong> - 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 be converted by CYP7B1 to 7α,25HC, a lipid with chemoattractant activity via the G protein-coupled receptor, EBI2/GPR183. Here, using in vitro studies and 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>Design of a bifunctional pan-sarbecovirus entry inhibitor targeting the cell receptor and viral fusion protein</strong> - Development of highly effective antivirals that are robust to viral evolution is a practical strategy for combating the continuously evolved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inspired by viral multistep entry process, we here focus on developing a bispecific SARS-CoV-2 entry inhibitor, which acts on the cell receptor angiotensin converting enzyme 2 (ACE2) and viral S2 fusion protein. First, we identified a panel of diverse spike (S) receptor-binding domains (RBDs) and…</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 novel robust inhibitor of papain-like protease (PLpro) as a COVID-19 drug</strong> - Regarding the significance of SARS-CoV-2, scientists have shown considerable interest in developing effective drugs. Inhibitors for PLpro are the primary strategies for locating suitable COVID-19 drugs. Natural compounds comprise the majority of COVID-19 drugs. Due to limitations on the safety of clinical trials in cases of COVID, computational methods are typically utilized for inhibition studies. Whereas papain is highly similar to PLpro and is entirely safe, the current study aimed to examine…</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>Growth media affects susceptibility of air-lifted human nasal epithelial cell cultures to SARS-CoV2, but not Influenza A, virus infection</strong> - Primary differentiated human epithelial cell cultures have been widely used by researchers to study viral fitness and virus-host interactions, especially during the COVID19 pandemic. These cultures recapitulate important characteristics of the respiratory epithelium such as diverse cell type composition, polarization, and innate immune responses. However, standardization and validation of these cultures remains an open issue. In this study, two different expansion medias were evaluated and 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>Protegrin-2, a potential inhibitor for targeting SARS-CoV-2 main protease M<sup>pro</sup></strong> - CONCLUSIONS: Our in silico and experimental studies identified Protegrin-2 as a potent inhibitor of M^(pro) that could be pursued further towards drug development against COVID-19 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>Real-world effectiveness of mRNA COVID-19 vaccines in the elderly during the Delta and Omicron variants: Systematic review</strong> - CONCLUSION: Because of the natural diminishing effectiveness of the vaccine, the need for booster dose to restore its efficacy is vital. From a research perspective, the use of highly heterogeneous outcome measures inhibits the comparison, contrast, and integration of the results which makes data pooling across different studies problematic. While pharmaceutical intervention like vaccination is important to fight an epidemic, utilizing common outcome measurements or carrying out studies with…</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 pan-coronavirus peptide inhibitor prevents SARS-CoV-2 infection in mice by intranasal delivery</strong> - Coronaviruses (CoVs) have brought serious threats to humans, particularly severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which continually evolves into multiple variants. These variants, especially Omicron, reportedly escape therapeutic antibodies and vaccines, indicating an urgent need for new antivirals with pan-SARS-CoV-2 inhibitory activity. We previously reported that a peptide fusion inhibitor, P3, targeting heptad repeated-1 (HR1) of SARS-CoV-2 spike (S) protein, could…</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>Age differential CD13 and interferon expression in airway epithelia affect SARS-CoV-2 infection - effects of vitamin D</strong> - Young age and high vitamin D plasma levels have been associated with lower SARS-CoV-2 infection risk and favourable disease outcomes. This study investigated mechanisms associated with differential responses to SARS-CoV-2 across age groups and effects of vitamin D. Nasal epithelia were collected from healthy children and adults and cultured for four weeks at air-liquid interface with and without vitamin D. Gene expression (NanoString) and DNA methylation (Illumina EPIC850K) were investigated….</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>Spike protein mutations and structural insights of pangolin lineage B.1.1.25 with implications for viral pathogenicity and ACE2 binding affinity</strong> - Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID -19, is constantly evolving, requiring continuous genomic surveillance. In this study, we used whole-genome sequencing to investigate the genetic epidemiology of SARS-CoV-2 in Bangladesh, with particular emphasis on identifying dominant variants and associated mutations. We used high-throughput next-generation sequencing (NGS) to obtain DNA sequences from COVID-19 patient samples and compared these…</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 of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase</strong> - The dual functions of TMEM16F as Ca^(2+)-activated ion channel and lipid scramblase raise intriguing questions regarding their molecular basis. Intrigued by the ability of the FDA-approved drug niclosamide to inhibit TMEM16F-dependent syncytia formation induced by SARS-CoV-2, we examined cryo-EM structures of TMEM16F with or without bound niclosamide or 1PBC, a known blocker of TMEM16A Ca^(2+)-activated Cl^(-) channel. Here, we report evidence for a lipid scrambling pathway along a groove…</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>CYP19A1 mediates severe SARS-CoV-2 disease outcome in males</strong> - Male sex represents one of the major risk factors for severe COVID-19 outcome. However, underlying mechanisms that mediate sex-dependent disease outcome are as yet unknown. Here, we identify the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (also known as aromatase) as a host factor that contributes to worsened disease outcome in SARS-CoV-2-infected males. We analyzed exome sequencing data obtained from a human COVID-19 cohort (n = 2,866) 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>Molnupiravir, a ribonucleoside antiviral prodrug against SARS-CoV-2, alters the voltage-gated sodium current and causes adverse events</strong> - Molnupiravir (MOL) is a ribonucleoside prodrug for oral treatment of COVID-19. Common adverse effects of MOL are headache, diarrhea, and nausea, which may be associated with altered sodium channel function. Here, we investigated the effect of MOL on voltage-gated Na^(+) current (I(Na)) in pituitary GH(3) cells. We show that MOL had distinct effects on transient and late I(Na), in combination with decreased time constant in the slow component of I(Na) inactivation. The 50% inhibitory…</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>Expression and immunogenicity of recombinant porcine epidemic diarrhea virus Nsp9</strong> - Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea, vomiting, dehydration, and high mortality in newborn piglets, which leads to significant economic losses. Coronavirus nonstructural protein 9 (Nsp9) is an essential RNA binding protein for coronavirus replication, which renders it a promising candidate for developing antiviral drugs and diagnosis targeting PEDV. In this study, PEDV Nsp9 protein fused with MBP protein and His-tag were expressed and purified in Escherichia coli….</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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