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162 lines
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<title>27 March, 2024</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>Inference of epidemic dynamics in the COVID-19 era and beyond</strong> -
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<div>
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The COVID-19 pandemic demonstrated the key role that epidemiology and modelling play in analysing infectious threats and supporting decision making in real-time. Motivated by the unprecedented volume and breadth of data generated during the pandemic, we review new analytic opportunities and methodological developments available to address questions that emerge during a major modern epidemic. Following the broad chronology of insights required - from understanding initial dynamics to retrospective evaluation of interventions, we describe the theoretical foundations of each approach and the underlying intuition. Through a series of case studies, we illustrate real life applications, and discuss implications for future work.
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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/bmjxf/" target="_blank">Inference of epidemic dynamics in the COVID-19 era and beyond</a>
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</div></li>
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<li><strong>Changes in values and well-being amidst the COVID-19 pandemic in Poland</strong> -
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<div>
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COVID-19 caused a global change in the lifestyles of people around the world. It provided a unique opportunity to examine how external circumstances impact two crucial aspects of functioning relating to “who I am” (values) and “how I feel” (well-being). Participants (N = 150) reported their values, subjective and eduaimonic well-being nine months before lockdown in Poland, two weeks and four weeks into lockdown. We observed significant changes in values: an increase in self-direction, achievement, security, conformity, humility, benevolence and universalism, and a decrease in hedonism. All well-being indices showed a decrease in well-being with one specific difference between men and women: women experienced a more significant increase of negative affect compared to men. Finally, we showed that Openness to change values predict lower negative affect and higher eudaimonic well-being two weeks into lockdown. This study is unique in that it shows, that well-being and individually held values are flexible and adaptive systems that react to external circumstances, such as global critical events.
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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/preprints/psyarxiv/xr87s/" target="_blank">Changes in values and well-being amidst the COVID-19 pandemic in Poland</a>
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</div></li>
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<li><strong>Social norms (not threat) mediate willingness to sacrifice in individuals fused with the nation</strong> -
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<div>
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Identity fusion with the community has been previously found to mediate altruism in post-disaster settings. However, whether this altruistic response is specifically triggered by ingroup threat, or whether it can also be triggered by global threats remains unclear. We evaluated willingness to sacrifice in the context of the covid-19 pandemic across three surveys waves. Against expectations, participants fused with the nation (vs. non-fused) did not differentially respond to a national vs. global threat condition. Conversely, social norms decisively influenced willingness to sacrifice in this sample, with fused individuals with stronger norms about social distancing reporting the highest altruistic response during the first weeks of the pandemic. Longitudinally, after an initial peak in the altruistic response, deteriorating social norms mediated decreases in willingness to sacrifice in individuals fused with the nation (versus non-fused). Implications of these results for the development of interventions aimed to address global challenges are discussed.
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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/preprints/psyarxiv/r6hf4/" target="_blank">Social norms (not threat) mediate willingness to sacrifice in individuals fused with the nation</a>
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</div></li>
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<li><strong>Chronumental: time tree estimation from very large phylogenies</strong> -
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<div>
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Phylogenetic trees are an important tool for interpreting sequenced genomes, and their interrelationships. Estimating the date associated with each node of such a phylogeny creates a “time tree”, which can be especially useful for visualising and analysing evolution of organisms such as viruses. Several tools have been developed for time-tree estimation, but the sequencing explosion in response to the SARS-CoV-2 pandemic has created phylogenies so large as to prevent the application of these previous approaches to full datasets. Here we introduce Chronumental, a tool that can rapidly infer time trees from phylogenies featuring large numbers of nodes. Chronumental uses stochastic gradient descent to identify lengths of time for tree branches which maximise the evidence lower bound under a probabilistic model, implemented in a framework which can be compiled into XLA for rapid computation. We show that Chronumental scales to phylogenies featuring millions of nodes, with chronological predictions made in minutes, and is able to accurately predict the dates of nodes for which it is not provided with metadata.
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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/10.1101/2021.10.27.465994v3" target="_blank">Chronumental: time tree estimation from very large phylogenies</a>
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</div></li>
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<li><strong>Unrestricted versus Regulated Open Data Governance: A Bibliometric Comparison of SARS-CoV-2 Nucleotide Sequence Databases</strong> -
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<div>
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Two distinct modes of data governance have emerged in accessing and reusing viral data pertaining to COVID-19: an unrestricted model, espoused by data repositories part of the International Nucleotide Sequence Database Collaboration and a regulated model promoted by the Global Initiative on Sharing All Influenza data. In this paper, we focus on publications mentioning either infrastructure in the period between January 2020 and January 2023, thus capturing a period of acute response to the COVID-19 pandemic. Through a variety of bibliometric and network science methods, we compare the extent to which either data infrastructure facilitated collaboration from different countries around the globe to understand how data reuse can enhance forms of diversity between institutions, countries, and funding groups. Our findings reveal disparities in representation and usage between the two data infrastructures. We conclude that both approaches offer useful lessons, with the unrestricted model providing insights into complex data linkage and the regulated model demonstrating the importance of global representation.
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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/10.1101/2023.05.13.540634v3" target="_blank">Unrestricted versus Regulated Open Data Governance: A Bibliometric Comparison of SARS-CoV-2 Nucleotide Sequence Databases</a>
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</div></li>
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<li><strong>Can we rely on trust in science to beat the COVID-19 pandemic?</strong> -
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<div>
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In order to provide time critical information on the social determinants of health during the COVID-19 pandemic, we relate levels of trust in science with government responses to the pandemic and the extent to which populations reduced mobility, a measure identified by epidemiologists as critical to halt the spread of the SARS-CoV-2 virus. We used data from the 2018 Wellcome Global Monitor to develop a comparable index of trust in science across 144 countries using confirmatory analysis models for categorical data (often referred as Item Response Models) with alignment optimisation. We use this index to provide evidence on the association between trust in science, country level mobility changes following the COVID-19 pandemic and the stringency of regulations to halt COVID-19 spread. We find that trust in science was highest in Nordic European countries, among individuals with high educational attainment and income. Differences by religiosity, gender and residency were less pronounced. Countries where individuals trust science the most enacted less stringent regulations in reaction to the COVID-19 pandemic than countries where individuals trust science the least. Irrespective of country-specific trust in science, behaviors such as mobility reductions changed the most in countries with more stringent regulations. Stringent regulations were associated with large reductions in mobility irrespective of levels of trust in science. By contrast, where regulations were less stringent, mobility decreased more in countries with lower levels of trust in science. Many governments are considering relaxing regulations that were put in place following the rapid surge of cases and deaths and the risk that health care systems would be overwhelmed. At the country level, higher levels of trust in science appear to be associated with less voluntary adoption of behaviors that could reduce transmission, such as mobility reductions.
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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/preprints/psyarxiv/yq287/" target="_blank">Can we rely on trust in science to beat the COVID-19 pandemic?</a>
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</div></li>
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<li><strong>The impact of COVID-19 on physical activity and mental health: A mixed-methods approach</strong> -
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<div>
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The global COVID-19 pandemic has negatively impacted people’s physical and mental health, and studies on ways to support people are scarce. This mixed-methods study investigated how and why physical activity (PA), anxiety, depression and self-perceived loneliness are related, and the feasibility of social prescribing in supporting individuals. Data from the UCL-Penn Global COVID Study wave 1 (17 April – 17 July 2020, N = 1,037) were analysed. Twenty-one UK adults who self-identified as low (n = 15) and high (n = 6) on PA at wave 1 were interviewed at wave 4 (18 March – 1 August 2022). At wave 1, depression was associated with higher odds of low-PA (OR = 1.05; 95% CI 1.01-1.10, p = .02). Both high/low-PA groups cited the threat of contracting coronavirus, general impacts of COVID-19 policies and heightened awareness of the mind-body connection. Findings detail practical and emotional challenges in engaging with social prescribing through clinical settings.
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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/64u7j/" target="_blank">The impact of COVID-19 on physical activity and mental health: A mixed-methods approach</a>
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</div></li>
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<li><strong>Influenza sequence validation and annotation using VADR</strong> -
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<div>
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Tens of thousands of influenza sequences are deposited into the GenBank database each year. The software tool FLAN has been used by GenBank since 2007 to validate and annotate incoming influenza sequence submissions, and has been publicly available as a webserver but not as a standalone tool. VADR is a general sequence validation and annotation software package used by GenBank for Norovirus, Dengue virus and SARS-CoV-2 virus sequence processing that is available as a standalone tool. We have created VADR influenza models based on the FLAN reference sequences and adapted VADR to accurately annotate influenza sequences. VADR and FLAN show consistent results on the vast majority of influenza sequences, and when they disagree VADR is usually correct. VADR can also accurately process influenza D sequences as well as influenza A H17, H18, H19, N10 and N11 subtype sequences, which FLAN cannot. VADR 1.6.3 and the associated influenza models are now freely available for users to download and use.
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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/10.1101/2024.03.21.585980v1" target="_blank">Influenza sequence validation and annotation using VADR</a>
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</div></li>
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<li><strong>System and transcript dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2)</strong> -
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<div>
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Statistical laws arise in many complex systems and can be explored to gain insights into their structure and behavior. Here, we investigate the dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2) at the system and individual gene levels; and demonstrate that the statistical frameworks used here are robust in spite of the technical noise associated with single-cell RNA sequencing (scRNA-seq) data. A biphasic fit to Taylor's power law was observed, and it is likely associated with the larger sampling noise inherent to the measure of less expressed genes. The type of the distribution of the system, as assessed by Taylor's parameters, varies along the course of infection in a cell type-dependent manner, but also sampling noise had a significant influence on Taylor's parameters. At the individual gene level, we found that genes that displayed signals of punctual rank stability and/or long-range dependence behavior, as measured by Hurst exponents, were associated with translation, cellular respiration, apoptosis, protein-folding, virus processes, and immune response.
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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/10.1101/2024.03.25.586528v1" target="_blank">System and transcript dynamics of cells infected with severe acute respiratory syndrome virus 2 (SARS-CoV-2)</a>
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</div></li>
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<li><strong>A human commons cell atlas reveals cell type specificity for OAS1 isoforms</strong> -
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<div>
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We describe an open source Human Commons Cell Atlas comprising 2.9 million cells across 27 tissues that can be easily updated and that is structured to facilitate custom analyses. To showcase the flexibility of the atlas, we demonstrate that it can be used to study isoforms of genes at cell resolution. In particular, we study cell type specificity of isoforms of OAS1, which has been shown to offer SARS-CoV-2 protection in certain individuals that display higher expression of the p46 isoform. Using our commons cell atlas we localize the OAS1 p44b isoform to the testis, and find that it is specific to round and elongating spermatids. By virtue of enabling customized analyses via a modular and dynamic atlas structure, the commons cell atlas should be useful for exploratory analyses that are intractable within the rigid framework of current gene-centric cell atlases.
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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/10.1101/2024.03.23.586412v1" target="_blank">A human commons cell atlas reveals cell type specificity for OAS1 isoforms</a>
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</div></li>
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<li><strong>Do abortion bans somehow save pregnant people’s lives? A cautionary research note on trends in maternal death post-Dobbs</strong> -
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<div>
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The National Center for Health Statistics’ published provisional monthly estimates of maternal death (12-month ending counts) appear to demonstrate that the end of federal protection for abortion rights in June 2022 was associated with an immediate and dramatic decline in maternal deaths. In this research note we investigate this apparent association by comparing the 12-month ending counts with monthly counts of maternal death. We decompose change in the 12-month ending counts into change due to months leaving the sum and change due to the current month entering the sum and conclude that the rapid decline in the 12-month ending counts is driven by events in 2021, specifically the shock to maternal deaths during the Delta and Omicron waves of the COVID-19 pandemic. Actual monthly final and provisional maternal deaths from the National Vital Statistics Surveillance System did not decline after June 2022. We caution that any analysis of change in maternal deaths should exercise extreme caution when using summed measures in general and the 12-month ending counts in particular.
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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/preprints/socarxiv/jtkqe/" target="_blank">Do abortion bans somehow save pregnant people’s lives? A cautionary research note on trends in maternal death post-Dobbs</a>
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</div></li>
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<li><strong>Online Data Collection in Applied Linguistics</strong> -
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<div>
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During the height of the COVID-19 pandemic, researchers became resourceful and many transitioned to online methods for remote data collection, suddenly bringing many platforms and methods to prominence in new experimental contexts. As in-person data collection resumed, online data collection remained as these methods have proven particularly useful in the field of applied linguistics and especially Second Language Acquisition (SLA), which often requires researchers to recruit participants who are inherently difficult to find (e.g., individuals proficient in less-commonly taught languages or living in a context far from the researcher’s university). In this chapter, we highlight factors that researchers should consider when implementing online research along with a high-level troubleshooting guide. We cover recruitment, enhancing participant performance, implementation, and deployment. Within these topics, we highlight important technological, procedural, and participant privacy recommendations for visual, aural, and oral online data collection designs specially tailored for applied linguists.
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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/pxfc4/" target="_blank">Online Data Collection in Applied Linguistics</a>
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</div></li>
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<li><strong>Identification of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro) for the Development of COVID-19 Antivirals</strong> -
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<div>
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Coronaviruses such as SARS-CoV-2 encode a conserved papain-like protease (PLpro) that is crucial for viral replication and immune evasion, making it a prime target for antiviral drug development. In this study, three surface pockets on SARS-CoV-2 PLpro that may function as sites for allosteric inhibition were computationally identified. To evaluate the effects of these pockets on proteolytic activity, 52 residues were separately mutated to alanine. In Pocket 1, located between the Ubl and thumb domains, the introduction of alanine at T10, D12, T54, Y72, or Y83 reduced PLpro activity to <12% of that of WT. In Pocket 2, situated at the interface of the thumb, fingers, and palm domains, Q237A, S239A, H275A, and S278A inactivated PLpro. Finally, introducing alanine at five residues in Pocket 3, between the fingers and palm domains, inactivated PLpro: S212, Y213, Y251, K254, and Y305. Pocket 1 has a higher druggability score than Pockets 2 and 3. MD simulations showed that interactions within and between domains play critical roles in PLpro activity and thermal stability. The essential residues in Pockets 1 and 2 participate in a combination of intra- and inter-domain interactions. By contrast, the essential residues in Pocket 3 predominantly participate in inter-domain interactions. The most promising targets for therapeutic development are Pockets 1 and 3, which have the highest druggability score and the largest number of essential residues, respectively. Non-competitive inhibitors targeting these pockets may be antiviral agents against COVID-19 and related coronaviruses.
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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/10.1101/2023.05.16.540953v3" target="_blank">Identification of Novel Allosteric Sites of SARS-CoV-2 Papain-Like Protease (PLpro) for the Development of COVID-19 Antivirals</a>
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</div></li>
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<li><strong>Neural networks built from enzymatic reactions can operate as linear and nonlinear classifiers</strong> -
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<div>
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The engineering of molecular programs capable of processing patterns of multi-input biomarkers holds great potential in applications ranging from in vitro diagnostics (e.g., viral detection, including COVID-19) to therapeutic interventions (e.g., discriminating cancer cells from normal cells). For this reason, mechanisms to design molecular networks for pattern recognition are highly sought after. In this work, we explore how enzymatic networks can be used for both linear and nonlinear classification tasks. By leveraging steady-state analysis and showing global stability, we demonstrate that these networks can function as molecular perceptrons, fundamental units of artificial neural networks-capable of processing multiple inputs associated with positive and negative weights to achieve linear classification. Furthermore, by composing orthogonal enzymatic reactions, we show that multi-layer networks can be constructed to achieve nonlinear classification.
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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/10.1101/2024.03.23.586372v1" target="_blank">Neural networks built from enzymatic reactions can operate as linear and nonlinear classifiers</a>
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</div></li>
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<li><strong>Neutralisation sensitivity of the SARS-CoV-2 BA.2.87.1 variant</strong> -
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<div>
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Against the backdrop of the rapid global takeover and dominance of BA.1/BA.2 and subsequently BA.2.86 lineages, the emergence of a highly divergent SARS-CoV-2 variant warrants characterization and close monitoring. Recently, another such BA.2 descendent, designated BA.2.87.1, was detected in South Africa. Here, we show using spike-pseudotyped viruses that BA.2.87.1 is less resistant to neutralisation by prevailing antibody responses in Sweden than other currently circulating variants such as JN.1. Further we show that a monovalent XBB.1.5-adapted booster enhanced neutralising antibody titers to BA.2.87.1 by almost 4-fold. While BA.2.87.1 may not outcompete other currently-circulating lineages, the repeated emergence and transmission of highly diverged variants suggests that another large antigenic shift, similar to the replacement by Omicron, may be likely in the future.
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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/10.1101/2024.03.21.586176v1" target="_blank">Neutralisation sensitivity of the SARS-CoV-2 BA.2.87.1 variant</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Diaphragmatic Breathing Exercises for Post-COVID-19 Diaphragmatic Dysfunction (DD)</strong> - <b>Conditions</b>: Post-Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Usual care of traditional treatment; Other: Specific DB program/Diaphragmatic manipulation program <br/><b>Sponsors</b>: University of Minnesota <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>Valacyclovir Plus Celecoxib for Post-Acute Sequelae of SARS-CoV-2</strong> - <b>Conditions</b>: Long COVID; PASC Post Acute Sequelae of COVID 19 <br/><b>Interventions</b>: Drug: Valacyclovir celecoxib dose 1; Drug: Valacyclovir celecoxib dose 2; Drug: Placebo <br/><b>Sponsors</b>: Bateman Horne Center <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>Supervised Computerized Active Program for People With Post-COVID Syndrome (SuperCAP Study)</strong> - <b>Conditions</b>: Post-COVID Condition <br/><b>Interventions</b>: Device: SuperCAP Program <br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Institut de Recerca de la SIDA IrsiCaixa; Germans Trias i Pujol Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Utilizing Novel Blood RNA Biomarkers as a Diagnostic Tool in the Identification of Long COVID-19</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Diagnostic Test: RNA Biomarker Blood Test <br/><b>Sponsors</b>: MaxWell Clinic, PLC <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>Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes</strong> - <b>Conditions</b>: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome <br/><b>Interventions</b>: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT) <br/><b>Sponsors</b>: Princess Nourah Bint Abdulrahman University <br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein</strong> - The novel coronavirus disease 2019 has stimulated the rapid development of new biological therapeutics to inhibit SARS-CoV-2 infection; however, this remains a challenging task. In a previous study using structural analysis, we revealed that human cyclophilin A inhibits the entry of SARS-CoV-2 into host cells by interfering with the interaction of the receptor-binding domain of the spike protein with angiotensin-converting enzyme 2 on the host cell surface, highlighting its potential for…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exosomes from senescent epithelial cells activate pulmonary fibroblasts via the miR-217-5p/Sirt1 axis in paraquat-induced pulmonary fibrosis</strong> - CONCLUSION: These findings highlight a potential strategy for the treatment of pulmonary fibrosis induced by PQ poisoning. Disrupting the communication between senescent epithelial cells and pulmonary fibroblasts, particularly by targeting the miR-217-5p/SIRT1/β-catenin axis, may be able to alleviate the effects of PQ poisoning on the lungs.</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>Predicting anti-COVID-19 potential: in silico analysis of Mauritine compound from Ziziphus-spina christi as a promising papain-like protease (PLpro) inhibitor</strong> - The COVID-19 pandemic caused by the SARS-CoV-2 virus, recognized by the World Health Organization (WHO), has led to 164,523,894 confirmed cases and 3,412,032 deaths globally as of May 20, 2021. SARS-CoV-2 encodes crucial proteases for its replication cycle, including the papain-like protease (PLpro), presenting a potential target for developing COVID-19 treatments. Mauritine, a cyclopeptide alkaloid found in the Ziziphus-spina christi plant, exhibits antiviral properties and was investigated for…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The antiviral potential of the antiandrogen enzalutamide and the viral-androgen signaling interplay in seasonal coronaviruses</strong> - 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 to treat prostate cancer, as a potential antiviral against the human coronaviruses which cause seasonal respiratory infections (HCoV-NL63, -229E, and -OC43)….</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>Potential use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition and prevention method in viral infection</strong> - Cellular lipid membranes serve as the primary barrier preventing viral infection of the host cell and provide viruses with a critical initial point of contact. Occasionally, viruses can utilize lipids as viral receptors. Viruses depend significantly on lipid rafts for infection at virtually every stage of their life cycle. The pivotal role that proprotein convertase subtilisin/kexin Type 9 (PCSK9) plays in cholesterol homeostasis and atherosclerosis, primarily by post-transcriptionally…</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>Phosphatidylserine-exposing extracellular vesicles in body fluids are an innate defence against apoptotic mimicry viral pathogens</strong> - Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, or semen. We previously identified that extracellular vesicles (EVs) in semen and saliva inhibit Zika virus infection. However, the antiviral spectrum and underlying mechanism remained unclear. Here we applied lipidomics and flow cytometry to show that these EVs expose phosphatidylserine (PS). By blocking PS receptors, targeted by Zika virus in the process of apoptotic mimicry, they interfere…</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>Diammonium Glycyrrhizinate Inhibited Inflammatory Response and Modulated Serum Metabolism in Poly(I:C)-induced Pneumonia Model Mice</strong> - Currently, the coronavirus disease 2019 (COVID-19) is becoming a serious threat to human health worldwide. Therefore, there is a great need to develop effective drugs against viral pneumonia. Diammonium glycyrrhizinate (DG), derived from Glycyrrhiza glabra L., has been demonstrated with significant anti-inflammatory properties. However, the therapeutic effects and mechanisms of DG on pneumonia require further clarification. In this study, mice received intratracheal injection 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>Solid-liquid distribution of SARS-CoV-2 in primary effluent of a wastewater treatment plant</strong> - Distributions of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and fecal viral biomarkers between solid and liquid phases of wastewater are largely unknown. Herein, distributions of SARS-CoV-2, Pepper Mild Mottle Virus (PMMoV), and F-RNA bacteriophage group II (FRNAPH-II) were determined by viral RNA RT-qPCR. Comparison of viral recovery using three conventional fractionation methods included membrane filtration, a combination of mid-speed centrifugation and membrane filtration,…</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>Recent advances in the therapeutic potential of nobiletin against respiratory diseases</strong> - CONCLUSIONS: With the wide range of pharmacological activities, high efficiency and low toxicity, nobiletin can be used as a potential agent for preventing and treating RDs. These findings will contribute to further research on the molecular mechanisms of nobiletin and facilitate in-depth studies on nobiletin at both preclinical and clinical levels for the treatment of RDs.</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>Lymphopenia associated with survivin and its downstream pathway in COVID-19 serving as a potential route in COVID-19 pathogenesis</strong> - CONCLUSION: The role of survivin and its related pathway was first discovered in the development of COVID-19 and may serve as a potential prognostic and therapeutic target.</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>Discovery of Covalent Lead Compounds Targeting 3CL Protease with a Lateral Interactions Spiking Neural Network</strong> - Covalent drugs exhibit advantages in that noncovalent drugs cannot match, and covalent docking is an important method for screening covalent lead compounds. However, it is difficult for covalent docking to screen covalent compounds on a large scale because covalent docking requires determination of the covalent reaction type of the compound. Here, we propose to use deep learning of a lateral interactions spiking neural network to construct a covalent lead compound screening model to quickly…</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>Establishment, Optimization and validation of a fluorescence polarization-based high-throughput screening assay targeting Cathepsin L inhibitors</strong> - Cathepsin L (CTSL), a lysosomal cysteine proteinase, is primarily dedicated to the metabolic turnover of intracellular proteins. It is involved in various physiological processes and contributes to pathological conditions such as viral infection, tumor invasion and metastasis, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, and other ailments. The coronavirus disease 2019 (COVID-19), with its rapid global spread and significant mortality, has been a worldwide…</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>C1q enables influenza hemagglutinin stem binding antibodies to block viral attachment and broadens the antibody escape repertoire</strong> - Antigenic drift, the gradual accumulation of amino acid substitutions in the influenza virus hemagglutinin (HA) receptor protein, enables viral immune evasion. Antibodies (Abs) specific for the drift-resistant HA stem region are a promising universal influenza vaccine target. Although anti-stem Abs are not believed to block viral attachment, here we show that complement component 1q (C1q), a 460-kilodalton protein with six Ab Fc-binding domains, confers attachment inhibition to anti-stem Abs 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>Molecular docking and molecular dynamic simulation-based phytoconstituents against SARS-CoV-2 with dual inhibition of the primary protease targets</strong> - A novel coronavirus has caused major health problems and is spreading globally. The main protease enzyme plays a significant role in the number of copies of ss-RNA produced during the proteolytic cleavage of polypeptides. This work aims to find possible dual inhibitors of the 3-Chymotrypsin-like proteases PDB-6W63 and 6LU7 which increase efficiency and faster inhibition activity. By using an in-silico technique, polyphenols are molecularly docked against these targets to inhibit protease…</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>N-Arylsulfonamide-based adenosine analogues to target RNA cap N7-methyltransferase nsp14 of SARS-CoV-2</strong> - RNA cap methylations have been shown to be crucial for the life cycle, replication, and infection of ssRNA viruses, as well as for evading the host’s innate immune system. Viral methyltransferases (MTases) therefore represent an attractive target for the development of compounds as tools and inhibitors. In coronaviruses, N7-methyltransferase function is localized in nsp14, which has become an increasingly important therapeutic target with the COVID-19 pandemic. In recent years, we have been…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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