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181 lines
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<title>29 November, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Expression and fusogenic activity of SARS CoV-2 Spike protein displayed in the HSV-1 Virion.</strong> -
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<div>
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Severe acute respiratory syndrome coronavirus (SARS-CoV) is a zoonotic pathogen that can cause severe respiratory disease in humans. The new SARS-CoV-2 is the cause of the current global pandemic termed coronavirus disease 2019 (COVID-19) that has resulted in many millions of deaths world-wide. The virus is a member of the Betacoronavirus family, its genome is a positive strand RNA molecule that encodes for many genes which are required for virus genome replication as well as for structural proteins that are required for virion assembly and maturation. A key determinant of this virus is the Spike (S) protein embedded in the virion membrane and mediates attachment of the virus to the receptor (ACE2). This protein also is required for cell-cell fusion (syncytia) that is an important pathogenic determinant. We have developed a pseudotyped herpes simplex virus type 1 (HSV-1) recombinant virus expressing S protein in the virion envelop. This virus has also been modified to express a Venus fluorescent protein fusion to VP16, a virion protein of HSV-1. The virus expressing Spike can enter cells and generates large multi-nucleated syncytia which are evident by the Venus fluorescence. The HSV-1 recombinant virus is genetically stable and virus amplification can be easily done by infecting cells. This recombinant virus provides a reproducible platform for Spike function analysis and thus adds to the repertoire of pseudotyped viruses expressing Spike.
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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/10.1101/2023.11.28.568860v1" target="_blank">Expression and fusogenic activity of SARS CoV-2 Spike protein displayed in the HSV-1 Virion.</a>
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</div></li>
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<li><strong>Streamlining Computational Fragment-Based Drug Discovery through Evolutionary Optimization Informed by Ligand-Based Virtual Prescreening</strong> -
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<div>
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Recent advancements in computational methods provide the promise of dramatically accelerating drug discovery. While mathematical modeling and machine learning have become vital in predicting drug-target interactions and properties, there is untapped potential in computational drug discovery due to the vast and complex chemical space. This paper advances a novel computational fragment-based drug discovery (FBDD) method called Fragments from Ligands Drug Discovery (FDSL-DD), which aims to streamline drug design by applying a two-stage optimization process informed by machine learning and evolutionary principles. In this approach, in silico screening identifies ligands from a vast library, which are then fragmentized while attaching specific attributes based on predicted binding affinity and interaction with the target sub-domain. This process both shrinks the search space and focuses on promising regions within it. The first optimization stage assembles these fragments into larger compounds using evolutionary strategies, and the second stage iteratively refines resulting compounds for enhanced bioactivity. The methodology is validated across three diverse protein targets involved in human solid cancers, bacterial antimicrobial resistance, and SARS-CoV-2 viral entry, demonstrating the approach's broad applicability. Using the proposed FDSL-DD and two-stage optimization approach yields high-affinity ligand candidates more efficiently than other state-of-the-art computational methods. Furthermore, a multiobjective optimization is presented that accounts for druglikeness while still producing potential candidate ligands with high binding affinity. In conclustion, the results demonstrate that integrating detailed chemical information with a constrained search framework can markedly optimize the initial drug discovery process, offering a more precise and efficient route to developing new therapeutics.
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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/10.1101/2023.11.27.568919v1" target="_blank">Streamlining Computational Fragment-Based Drug Discovery through Evolutionary Optimization Informed by Ligand-Based Virtual Prescreening</a>
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</div></li>
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<li><strong>Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</strong> -
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<div>
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Since the start of the SARS-CoV-2 pandemic, the search for antiviral therapies has been at the forefront of medical research. To date, the 3CLpro inhibitor nirmatrelvir (Paxlovid) has shown the best results in clinical trials and the greatest robustness against variants. A second SARS-CoV-2 protease inhibitor, ensitrelvir (Xocova), has been developed. Ensitrelvir, currently in Phase 3, was approved in Japan under the emergency regulatory approval procedure in November 2022, and is available since March 31, 2023. One of the limitations for the use of antiviral monotherapies is the emergence of resistance mutations. Here, we experimentally generated mutants resistant to nirmatrelvir and ensitrelvir in vitro following repeating passages of SARS-CoV-2 in the presence of both antivirals. For both molecules, we demonstrated a loss of sensitivity for resistance mutants in vitro. Using a Syrian golden hamster infection model, we showed that the ensitrelvir M49L mutation confers a high level of in vivo resistance. Finally, we identified a recent increase in the prevalence of M49L-carrying sequences, which appears to be associated with multiple repeated emergence events in Japan and may be related to the use of Xocova in the country since November 2022. These results highlight the strategic importance of genetic monitoring of circulating SARS-CoV-2 strains to ensure that treatments administered retain their full effectiveness.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.22.568013v1" target="_blank">Generation and evaluation of protease inhibitor-resistant SARS-CoV-2 strains</a>
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</div></li>
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<li><strong>Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</strong> -
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<div>
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Since the emergence of SARS-CoV-2 in Wuhan in 2019 its host reservoir has not been established. Phylogenetic analysis was performed on whole genome sequences (WGS) of 71 coronaviruses and a Breda virus. A subset comprising two SARS-CoV-2 Wuhan viruses and 8 of the most closely related coronavirus sequences were used for host reservoir analysis using Bayesian Evolutionary Analysis Sampling Trees (BEAST). Within these genomes, 20 core genome fragments were combined into 2 groups each with similar clock rates (5.9x10 -3 and 1.1x10 -3 subs/site/year). Pooling the results from these fragment groups yielded a most recent common ancestor (MRCA) shared between SARS-COV-2 and the bat isolate RaTG13 around 2007 (95% HPD: 2003, 2011). Further, the host of the MRCA was most likely a bat (probability 0.64 - 0.87). Hence, the spillover into humans must have occurred at some point between 2007 and 2019 and bats may have been the most likely host reservoir.
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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/10.1101/2023.11.25.568670v1" target="_blank">Identification of the host reservoir of SARS-CoV-2 and determining when it spilled over into humans</a>
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</div></li>
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<li><strong>XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants</strong> -
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COVID-19 vaccines have recently been updated with the spike protein of SARS-Co-V-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine (XBB.1.5 MV) to uninfected individuals boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold). In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,764-to-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines to further protect the public.
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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/10.1101/2023.11.26.568730v1" target="_blank">XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against emerging SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>Variant- and Vaccination-Specific Alternative Splicing Profiles in SARS-CoV-2 Infections</strong> -
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<div>
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The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, and its subsequent variants has underscored the importance of understanding the host-viral molecular interactions to devise effective therapeutic strategies. A significant aspect of these interactions is the role of alternative splicing in modulating host responses and viral replication mechanisms. Our study sought to delineate the patterns of alternative splicing of RNAs from immune cells across different SARS-CoV-2 variants and vaccination statuses, utilizing a robust dataset of 190 RNA-seq samples from our previous studies, encompassing an average of 212 million reads per sample. We identified a dynamic alteration in alternative splicing and genes related to RNA splicing were highly deactivated in COVID-19 patients and showed variant- and vaccination-specific expression profiles. Overall, Omicron-infected patients exhibited a gene expression profile akin to healthy controls, unlike the Alpha or Beta variants. However, significantly, we found identified a subset of infected individuals, most pronounced in vaccinated patients infected with Omicron variant, that exhibited a specific dynamic in their alternative splicing patterns that was not widely shared amongst the other groups. Our findings underscore the complex interplay between SARS-CoV-2 variants, vaccination-induced immune responses, and alternative splicing, emphasizing the necessity for further investigations into these molecular cross-talks to foster deeper understanding and guide strategic therapeutic development.
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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/10.1101/2023.11.24.568603v1" target="_blank">Variant- and Vaccination-Specific Alternative Splicing Profiles in SARS-CoV-2 Infections</a>
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<li><strong>Evolution-guided large language model is a predictor of virus mutation trends</strong> -
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<div>
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Emerging viral infections, especially the global pandemic COVID-19, have had catastrophic impacts on public health worldwide. The culprit of this pandemic, SARS-CoV-2, continues to evolve, giving rise to numerous sublineages with distinct characteristics. The traditional post-hoc wet-lab approach is lagging behind, and it cannot quickly predict the evolutionary trends of the virus while consuming high costs. Capturing the evolutionary drivers of virus and predicting potential high-risk mutations has become an urgent and critical problem to address. To tackle this challenge, we introduce ProtFound-V, an evolution-inspired deep-learning framework designed to explore the mutational trajectory of virus. Take SARS-CoV-2 as an example, ProtFound-V accurately identifies the evolutionary advantage of Omicron and proposes evolutionary trends consistent with wet-lab experiments through in silico deep mutational scanning. This showcases the potential of deep learning predictions to replace traditional wet-lab experimental measurements. With the evolution-guided large language model, ProtFound-V presents a new state-of-the-art performance in key property predictions. Despite the challenge posed by epistasis to model generalization, ProtFound-V remains robust when extrapolating to lineages with different genetic backgrounds. Overall, this work paves the way for rapid responses to emerging viral infections, allowing for a plug-and-play approach to understanding and predicting virus evolution.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.27.568815v1" target="_blank">Evolution-guided large language model is a predictor of virus mutation trends</a>
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</div></li>
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<li><strong>Modulation of human kinase activity through direct interaction with SARS-CoV-2 proteins</strong> -
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<div>
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The dysregulation of cellular signaling upon SARS-CoV-2 infection is mediated via direct protein interactions, with the human protein kinases constituting the major impact nodes in the signaling networks. Here, we employed a targeted yeast two-hybrid matrix approach to identify direct SARS-CoV-2 protein interactions with an extensive set of human kinases. We discovered 51 interactions involving 14 SARS-CoV-2 proteins and 29 human kinases, including many of the CAMK and CMGC kinase family members, as well as non-receptor tyrosine kinases. By integrating the interactions identified in our screen with transcriptomics and phospho-proteomics data, we revealed connections between SARS-CoV-2 protein interactions, kinase activity changes, and the cellular phospho-response to infection and identified altered activity patterns in infected cells for AURKB, CDK2, CDK4, CDK7, ABL2, PIM2, PLK1, NEK2, TRIB3, RIPK2, MAPK13, and MAPK14. Finally, we demonstrated direct inhibition of the FER human tyrosine kinase by the SARS-CoV-2 auxiliary protein ORF6, hinting at pressures underlying ORF6 changes observed in recent SARS-CoV-2 strains. Our study expands the SARS-CoV-2 - host interaction knowledge, illuminating the critical role of dysregulated kinase signaling during SARS-CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.27.568816v1" target="_blank">Modulation of human kinase activity through direct interaction with SARS-CoV-2 proteins</a>
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<li><strong>Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection.</strong> -
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Pathogen encounter results in long-lasting epigenetic imprinting that shapes diseases caused by heterologous pathogens. The breadth of this innate immune memory is of particular interest in the context of respiratory pathogens with increased pandemic potential and wide-ranging impact on global health. Here, we investigated epigenetic imprinting across cell lineages in a disease relevant murine model of SARS-CoV-2 recovery. Past SARS-CoV-2 infection resulted in increased chromatin accessibility of type I interferon (IFN-I) related transcription factors in airway-resident macrophages. Mechanistically, establishment of this innate immune memory required viral pattern recognition and canonical IFN-I signaling and augmented secondary antiviral responses. Past SARS-CoV-2 infection ameliorated disease caused by the heterologous respiratory pathogen influenza A virus. Insights into innate immune memory and how it affects subsequent infections with heterologous pathogens to influence disease pathology could facilitate the development of broadly effective therapeutic strategies.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.24.568354v1" target="_blank">Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection.</a>
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<li><strong>The antiviral potential of the antiandrogen enzalutamide and the viral-androgen interplay in seasonal coronaviruses</strong> -
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The sex disparity in COVID-19 outcomes with males generally faring worse than females has been associated with the androgen-regulated expression of the protease TMPRSS2 and the cell receptor ACE2 in the lung and fueled interest in antiandrogens as potential antivirals. In this study, we explored enzalutamide, an antiandrogen used commonly against prostate cancer, as a potential antiviral against the human coronaviruses which cause seasonal respiratory infections (HCoV-NL63, -229E, and -OC43). Using lentivirus-pseudotyped and authentic HCoV, we report that enzalutamide reduced 229E and NL63 entry and replication in both TMPRSS2- and non-expressing immortalised cells, suggesting a TMPRSS2-independent mechanism. However, no effect was observed against OC43. To decipher this distinction, we performed RNA-sequencing analysis on 229E- and OC43-infected primary human airway cells. Our results show a significant induction of androgen-responsive genes by 229E compared to OC43 at 24 and 72h post-infection. The virus-mediated effect to AR signaling was further confirmed with a consensus androgen response element (ARE)-driven luciferase assay in androgen-depleted MRC-5 cells. Specifically, 229E induced luciferase reporter activity in the presence and absence of the synthetic androgen mibolerone, while OC43 inhibited induction. These findings highlight a complex interplay between viral infections and androgen signaling, offering insights for potential antiviral interventions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.25.568685v1" target="_blank">The antiviral potential of the antiandrogen enzalutamide and the viral-androgen interplay in seasonal coronaviruses</a>
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<li><strong>Hybrid Course Dynamics in Physical Education: Insights from a Leading Chinese Public University</strong> -
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Against the backdrop of technological advances, educational reforms, and the impact of the COVID-19 pandemic, hybrid courses have become increasingly popular in higher education in China. The study draws from existing theoretical knowledge and practical experiences to provide insights on the feasibility and potential benefits of using the hybrid course modality in physical education, aiming to investigate the applicability of the hybrid course modality in promoting undergraduate students’ engagement in physical education courses at a large public university in China. It also focuses on practical implications of the hybrid course modality to enhance physical education courses in Chinese higher education institutions, by exploring how this modality can serve as a useful tool in such courses.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/edarxiv/hcevw/" target="_blank">Hybrid Course Dynamics in Physical Education: Insights from a Leading Chinese Public University</a>
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<li><strong>SARS-CoV-2 sequencing with cloud-based analysis illustrates expedient co-ordinated surveillance of viral genomic epidemiology across six continents</strong> -
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Viral sequencing has been critical in the COVID-19 pandemic response, but sequencing and bioinformatics capacity remain inconsistent. To examine the utility of a cloud-based sequencing analysis platform for SARS-CoV-2 sequencing, we conducted a cross-sectional study incorporating seven countries in July 2022. Sites submitted sequential SARS-CoV-2 sequences over two weeks to the Global Pathogen Analysis Service (GPAS). The GPAS bioinformatics cloud platform performs sequence assembly plus lineage and related sample identification. Users can share information with collaborators while retaining data ownership. Seven sites contributed sequencing reads from 5,346 clinical samples, of which 4,799/5,346 (89.8%) had a lineage identified. Omicron lineages dominated, with the vast majority being BA.5, BA.4 and BA.2, commensurate with contemporary genomic epidemiological observations. Phylogenetic analysis demonstrated low within-lineage diversity, and highly similar sequences present in globally disparate sites. A cloud-based analysis platform like GPAS addresses bioinformatics bottlenecks and facilitates collaboration in pathogen surveillance, enhancing epidemic and pandemic preparedness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.27.23298986v1" target="_blank">SARS-CoV-2 sequencing with cloud-based analysis illustrates expedient co-ordinated surveillance of viral genomic epidemiology across six continents</a>
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<li><strong>Characteristics of SARS-CoV-2 reinfection with Omicron BA.2.75 subvariants in Thai Adults.</strong> -
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Omicron subvariants of SARS-CoV-2 may resist vaccine- or infection-induced immunity thereby increasing the risk of reinfections in previously infected persons. This study aimed to investigate the clinical severity and the average time to the onset of Omicron reinfection. This survey study collected clinical data on Omicron reinfection. Information on time of infection, reinfection interval, overall clinical presentation, and severity of infection was reported. The total prevalence of symptoms among 201 participants was significantly higher in the first infection (risk difference (RD), 9.86%; 95% CI, 7.54-12.19]) compared to the second infection, and the hospitalization rate among all participants was significantly lower for the second infection than the primary infection (odds ratio (OR), 6.25; 95% CI, 2.158-24.71). The prevalence of symptoms compared with the first infection with pre-Omicron variants was similar to that of the first infection with the Omicron variant (RD, 2.56%; 95% CI, -6.14-1.01). However, the hospitalization rate for pre-Omicron primary infection was significantly higher (OR, 6.76; 95% CI, 2.87-15.87]) than that observed with Omicron variants. The severity of the primary infection and of a pre-Omicron variant was greater than that of a secondary infection or with an Omicron variant.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.24.23298841v1" target="_blank">Characteristics of SARS-CoV-2 reinfection with Omicron BA.2.75 subvariants in Thai Adults.</a>
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<li><strong>Genetic determinants of blood gene expression and splicing and their contribution to molecular phenotypes and health outcomes</strong> -
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The biological mechanisms through which most non-protein-coding genetic variants affect disease risk are unknown. To investigate the gene-regulatory cascades that ensue from these variants, we mapped blood gene expression and splicing quantitative trait loci (QTLs) through bulk RNA-sequencing in 4,732 participants, and integrated these data with protein, metabolite and lipid QTLs in the same individuals. We identified cis-QTLs for the expression of 17,233 genes and 29,514 splicing events (in 6,853 genes). Using colocalization analysis, we identified 3,430 proteomic and metabolomic traits with a shared association signal with either gene expression or splicing. We quantified the relative contribution of the genetic effects at loci with shared etiology through statistical mediation, observing 222 molecular phenotypes significantly mediated by gene expression or splicing. We uncovered gene-regulatory mechanisms at GWAS disease loci with therapeutic implications, such as WARS1 in hypertension, IL7R in dermatitis and IFNAR2 in COVID-19. Our study provides an open-access and interactive resource of the shared genetic etiology across transcriptional phenotypes, molecular traits and health outcomes in humans (https://IntervalRNA.org.uk).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.25.23299014v1" target="_blank">Genetic determinants of blood gene expression and splicing and their contribution to molecular phenotypes and health outcomes</a>
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<li><strong>Early warning system using primary healthcare data in the post-COVID-19-pandemic era: Brazil nationwide case-study</strong> -
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Background: Syndromic surveillance utilising primary health care (PHC) data is a valuable tool for early outbreak detection, as demonstrated in the potential to identify COVID-19 outbreaks. However, the potential of such an early warning system in the post-COVID-19 era remains largely unexplored. Methods: We analysed PHC encounter counts due to respiratory complaints registered in the Brazilian database of the Universal Health System between January and July 2023. We applied EARS (variation C1-C2-C3) and EVI to estimate the weekly thresholds. An alarm was determined when the number of encounters exceeded the week-specific threshold. We used data on hospitalisation due to respiratory disease to classify weeks in which the number of cases surpassed predetermined thresholds as anomalies. We compared EARS and EVI9s efficacy in anticipating anomalies. Findings: A total of 119 anomalies were identified across 116 immediate regions during the study period. The EARS-C2 presented the highest early alarm rate, with 81/119 (68%) early alarms, and C1 the lowest, with 71 (60%) early alarms. The lowest true positivity was the EARS-C1 118/1354 (8.7%) and the highest EARS-C3 99/856 (11.6%). Conclusion: Routinely collected PHC data can be successfully used to detect respiratory disease outbreaks in Brazil. Syndromic surveillance enhances timeliness in surveillance strategies, albeit with lower specificity. A combined approach with other strategies is essential to strengthen accuracy, offering a proactive and effective public health response against future outbreaks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.24.23299005v1" target="_blank">Early warning system using primary healthcare data in the post-COVID-19-pandemic era: Brazil nationwide case-study</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>Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Metformin; Other: Placebo <br/><b>Sponsors</b>: Trust for Vaccines and Immunization, Pakistan <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 Randomized Trial Evaluating a mRNA VLP Vaccine’s Immunogenicity and Safety for COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: AZD9838; Biological: Licensed mRNA vaccine <br/><b>Sponsors</b>: AstraZeneca <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 Effect of Aerobic Exercise and Strength Training on Physical Activity Level, Quality of Life and Anxiety-Stress Disorder in Young Adults With and Without Covid-19”</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Aerobic Exercise and Strength Training <br/><b>Sponsors</b>: Pamukkale University <br/><b>Active, not 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>Vale+Tú Salud: Corner-Based Randomized Trial to Test a Latino Day Laborer Program Adapted to Prevent COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Group Problem Solving; Behavioral: Standard of Care; Behavioral: Booster session <br/><b>Sponsors</b>: The University of Texas Health Science Center, Houston; National Institute on Minority Health and Health Disparities (NIMHD) <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>Safety Study of SLV213 for the Treatment of COVID-19.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Placebo for SLV213; Drug: SLV213 <br/><b>Sponsors</b>: National Institute of Allergy and Infectious Diseases (NIAID) <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>Collection of Additional Biological Samples From Potentially COVID-19 Patients for Monitoring of Biological Parameters Carried Out as Part of the Routine</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Diagnostic Test: RIPH2 <br/><b>Sponsors</b>: CerbaXpert <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>Promoting Engagement and COVID-19 Testing for Health</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: COVID-19 Test Reporting; Behavioral: Personalized Nudges via Text Messaging; Behavioral: Non-personalized Nudges via Text Messaging <br/><b>Sponsors</b>: Emory University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Morehouse School of Medicine; Georgia Institute of Technology <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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19 <br/><b>Interventions</b>: Behavioral: Individual counseling; Behavioral: Group counseling; Other: Resources <br/><b>Sponsors</b>: Idaho State 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>Development and Qualification of Methods for Analyzing the Mucosal Immune Response to COVID-19</strong> - <b>Conditions</b>: Certain Disorders Involving the Immune Mechanism <br/><b>Interventions</b>: Biological: Sampling; Biological: PCR (polymerase chain reaction) SARS-CoV-2 <br/><b>Sponsors</b>: University Hospital, Tours <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>Water-based Activity to Enhance Recovery in Long COVID</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Behavioral: WATER+CT; Behavioral: Usual Care <br/><b>Sponsors</b>: VA Office of Research and Development <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>Performance Evaluation of the Lucira COVID-19 & Flu Test</strong> - <b>Conditions</b>: COVID-19; Influenza <br/><b>Interventions</b>: Device: Lucira COVID-19 & Flu Test <br/><b>Sponsors</b>: Lucira Health Inc <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>Efficacy of Two Therapeutic Exercise Modalities for Patients With Persistent COVID</strong> - <b>Conditions</b>: Persistent COVID-19 <br/><b>Interventions</b>: Other: exercise programe <br/><b>Sponsors</b>: Facultat de ciencies de la Salut Universitat Ramon Llull <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>Robotic Assisted Hand Rehabilitation Outcomes in Adults After COVID-19</strong> - <b>Conditions</b>: Robotic Exoskeleton; Post-acute Covid-19 Syndrome; Rehabilitation Outcome; Physical And Rehabilitation Medicine <br/><b>Interventions</b>: Device: Training with a Robotic Hand Exoskeleton <br/><b>Sponsors</b>: University of Valladolid; Centro Hospitalario Padre Benito Menni <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>Cognitive Rehabilitation in Post-COVID-19 Syndrome</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Behavioral: CO-OP Procedures; Behavioral: Inactive Control Group <br/><b>Sponsors</b>: University of Missouri-Columbia; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) <br/><b>Not yet 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>Potential Targets and Mechanisms of Bitter Almond-Licorice for COVID-19 Treatment Based on Network Pharmacology and Molecular Docking</strong> - CONCLUSION: The bitter almond-licorice could be used to treat COVID-19 by inhibiting inflammatory responses and regulating cellular stress. This work is based on data mining and molecular docking, and the findings need to be interpreted with caution.</p>
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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>Resurrection of 2’-5’-oligoadenylate synthetase 1 (OAS1) from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication</strong> - The prenylated form of the human 2’-5’-oligoadenylate synthetase 1 (OAS1) protein has been shown to potently inhibit the replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. However, the OAS1 orthologue in the horseshoe bats (superfamily Rhinolophoidea), the reservoir host of SARS-related coronaviruses (SARSr-CoVs), has lost the prenylation signal required for this antiviral activity. Herein, we…</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>Neutrophil virucidal activity against SARS-CoV-2 is mediated by NETs</strong> - CONCLUSION: Our results provide evidence of the role of NETosis as a mechanism of SARS-CoV-2 viral capture and inhibition.</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 computational simulation appraisal of banana lectin as a potential anti-SARS-CoV-2 candidate by targeting the receptor-binding domain</strong> - CONCLUSIONS: These results confirm that the BanLec protein is a promising candidate for developing a potential therapeutic agent for combating COVID-19. Furthermore, the results suggest the possibility of BanLec as a broad-spectrum antiviral agent and highlight the need for further studies to examine the protein’s safety and effectiveness as a potent antiviral agent.</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 nsp15 endoribonuclease antagonizes dsRNA-induced antiviral signaling</strong> - Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has caused millions of deaths since emerging in 2019. Innate immune antagonism by lethal CoVs such as SARS-CoV-2 is crucial for optimal replication and pathogenesis. The conserved nonstructural protein 15 (nsp15) endoribonuclease (EndoU) limits activation of double-stranded (ds)RNA-induced pathways, including interferon (IFN) signaling, protein kinase R (PKR), and oligoadenylate synthetase/ribonuclease L (OAS/RNase L) during diverse CoV…</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>Application of machine learning models to identify serological predictors of COVID-19 severity and outcomes</strong> - Critically ill people with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. In 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody…</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>C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?</strong> - From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement…</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>Catalytic Antibodies May Contribute to Demyelination in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome</strong> - Here we report preliminary data demonstrating that some patients with myalgic encephalomyelitis/chronic fatiguesyndrome (ME/CFS) may have catalytic autoantibodies that cause the breakdown of myelin basic protein (MBP). We propose that these MBP-degradative antibodies are important to the pathophysiology of ME/CFS, particularly in the occurrence of white matter disease/demyelination. This is supported by magnetic resonance imagining studies that show these findings in patients with ME/CFS 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>Achievement Emotions of Medical Students: Do They Predict Self-regulated Learning and Burnout in an Online Learning Environment?</strong> - BACKGROUND: Achievement emotions have been proven as important indicators of students’ academic performance in traditional classrooms and beyond. In the online learning contexts, previous studies have indicated that achievement emotions would affect students’ adoption of self-regulated learning strategies and further predict their learning outcomes. However, the pathway regarding how different positive and negative achievement emotions might affect students’ burnout through self-regulated…</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>Linoleic acid: a natural feed compound against porcine epidemic diarrhea disease</strong> - Porcine epidemic diarrhea virus (PEDV) is a pig coronavirus that causes severe diarrhea and high mortality in piglets, but as no effective drugs are available, this virus threatens the pig industry. Here, we found that the intestinal contents of specific pathogen-free pigs effectively blocked PEDV invasion. Through proteomic and metabolic analyses of the intestinal contents, we screened 10 metabolites to investigate their function and found that linoleic acid (LA) significantly inhibited PEDV…</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>Platelet factor 4(PF4) and its multiple roles in diseases</strong> - Platelet factor 4 (PF4) combines with heparin to form an antigen that could produce IgG antibodies and participate in heparin-induced thrombocytopenia (HIT). PF4 has attracted wide attention due to its role in novel coronavirus vaccine-19 (COVID-9)-induced immune thrombotic thrombocytopenia (VITT) and cognitive impairments. The electrostatic interaction between PF4 and negatively charged molecules is vital in the progression of VITT, which is similar to HIT. Emerging evidence suggests its…</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 MERS-CoV entry inhibitory short peptides based on helix-stabilizing strategies</strong> - Interaction between Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) protein heptad repeat-1 domain (HR1) and heptad repeat-2 domain (HR2) is critical for the MERS-CoV fusion process. This interaction is mediated by the α-helical region from HR2 and the hydrophobic groove in a central HR1 trimeric coiled coil. We sought to develop a short peptidomimetic to act as a MERS-CoV fusion inhibitor by reproducing the key recognition features of HR2 helix. This was achieved by the use 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>A phenothiazine urea derivative broadly inhibits coronavirus replication via viral protease inhibition</strong> - Coronavirus (CoV) replication requires efficient cleavage of viral polyproteins into an array of non-structural proteins involved in viral replication, organelle formation, viral RNA synthesis, and host shutoff. Human CoVs (HCoVs) encode two viral cysteine proteases, main protease (M^(pro)) and papain-like protease (PL^(pro)), that mediate polyprotein cleavage. Using a structure-guided approach, a phenothiazine urea derivative that inhibits both SARS-CoV-2 M^(pro) and PL^(pro) protease activity…</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>Inhibition of furin-like enzymatic activities and SARS-CoV-2 infection by osthole and phenolic compounds with aryl side chains</strong> - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread as a pandemic and caused damage to people’s lives and countries’ economies. The spike (S) protein of SARS-CoV-2 contains a cleavage motif, Arg-X-X-Arg, for furin and furin-like enzymes at the boundary of the S1/S2 subunits. Given that cleavage plays a crucial role in S protein activation and viral entry, the cleavage motif was selected as the target. Our previous fluorogenic…</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>Efficient SARS-CoV-2 infection antagonization by rhACE2 ectodomain multimerized onto the Avidin-Nucleic-Acid-NanoASsembly</strong> - Nanodecoy systems based on analogues of viral cellular receptors assembled onto fluid lipid-based membranes of nano/extravescicles are potential new tools to complement classic therapeutic or preventive antiviral approaches. The need for lipid-based membranes for transmembrane receptor anchorage may pose technical challenges along industrial translation, calling for alternative geometries for receptor multimerization. Here we developed a semisynthetic self-assembling SARS-CoV-2 nanodecoy by…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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