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166 lines
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<title>24 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>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 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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<li><strong>Design of Antigen-Specific Antibody CDRH3 Sequences Using AI and Germline-Based Templates</strong> -
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<div>
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Antibody-antigen specificity is engendered and refined through a number of complex B cell processes, including germline gene recombination and somatic hypermutation. Here, we present an AI-based technology for de novo generation of antigen-specific antibody CDRH3 sequences using germline-based templates, and validate this technology through the generation of antibodies against SARS-CoV-2. AI-based processes that mimic the outcome, but bypass the complexity of natural antibody generation, can be efficient and effective alternatives to traditional experimental approaches for antibody discovery.
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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/10.1101/2024.03.22.586241v1" target="_blank">Design of Antigen-Specific Antibody CDRH3 Sequences Using AI and Germline-Based Templates</a>
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</div></li>
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<li><strong>The influence of COVID-19 fear beliefs on the relationships between positive mood and loss-of-control eating: a ten-day diary study</strong> -
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<div>
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Loss-of-control eating (LOCE) is driven by mood, and prevalence increased following onset of coronavirus 2019 (COVID-19). COVID-19 is associated with many stressors, including fear of illness, which could potentiate a relationship between mood and LOCE. Additionally, daily protective strategies to prevent contagion may be associated with LOCE, in line with ego depletion theory. Adults (N = 108) completed a 10-day diary study regarding LOCE, positive and negative mood, and protective behaviors. Participants rated COVID fear beliefs at a baseline assessment, hypothesized to predict LOCE directly between-subjects and have a cross-level interactive effect within-subjects. Data were analyzed with a multilevel model. Negative mood was associated with LOCE at both levels, although protective behaviors evinced no significant associations. Positive mood lacked significant direct association with LOCE, although there was an interactive effect such that there was an inverse association at low fear beliefs. Directions for future research and clinical implications 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/ta659/" target="_blank">The influence of COVID-19 fear beliefs on the relationships between positive mood and loss-of-control eating: a ten-day diary study</a>
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</div></li>
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<li><strong>Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants</strong> -
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<div>
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Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. We characterized the memory B-cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, and compared the immunogenicity with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one-month after a monovalent, BA.1 or BA.5 bivalent fourth dose COVID-19 vaccine. RBD-specific Bmem were quantified with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. All recipients had slightly increased WH1 RBD-specific Bmem numbers. Recognition of Omicron subvariants was not enhanced following monovalent vaccination, while both bivalent vaccines significantly increased WH1 RBD-specific Bmem cross-recognition of all Omicron subvariants tested by flow cytometry. Thus, Omicron-based bivalent vaccines can improve recognition of descendent Omicron subvariants by pre-existing, WH1-specific Bmem, beyond that of a conventional, monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants.
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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/10.1101/2024.03.20.585861v1" target="_blank">Bivalent COVID-19 vaccines boost the capacity of pre-existing SARS-CoV-2-specific memory B cells to cross-recognize Omicron subvariants</a>
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</div></li>
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<li><strong>Power users: Technology and Canadian sex workers during COVID-19</strong> -
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<div>
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The transition from physical to online advertising by sex workers in Canada has been well documented. However, few studies use rigorous sampling methods. This study considers how a technically sophisticated group of advertisers from a large Canadian sex work classifieds site used multiple online resources to promote or provide services during the COVID-19 pandemic. Advertisers qualified for the study if they used a URL as part of their contact information and were actively advertising between August 23 and September 22, 2022. A random sample of 1000 qualifying advertisers were selected of which 783 had accessible contact URLs. Themes were identified in downloaded website texts using grounded theory analysis. Ad metadata was used to identify demographic and behavioral distinctions between the sample and other advertisers. Almost all sampled advertisers (99%) provided in person services and most (70%) provided online services. The sample advertised more frequently, were more affluent and were more likely to be Anglophone, White, trans-female, or provide BDSM services. Themes of security, health, identity, and social networks were identified. Advertisers emphasized physical, emotional, and financial security. Most workers did not work in isolation and many participated in extensive social networks.
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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/u5kd2/" target="_blank">Power users: Technology and Canadian sex workers during COVID-19</a>
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</div></li>
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<li><strong>Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2</strong> -
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<div>
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Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also exhibiting functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
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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/10.1101/2023.11.21.568093v2" target="_blank">Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2</a>
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</div></li>
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<li><strong>SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids</strong> -
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<div>
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SARS-CoV-2 provokes devastating tissue damage by cytokine release syndrome and leads to multi-organ failure. Modeling the process of immune cell activation and subsequent tissue damage is a significant task. Organoids from human tissues advanced our understanding of SARS-CoV-2 infection mechanisms though, they are missing crucial components: immune cells and endothelial cells. This study aims to generate organoids with these components. We established vascular immune organoids from human pluripotent stem cells and examined the effect of SARS-CoV-2 infection. We demonstrated that infections activated inflammatory macrophages. Notably, the upregulation of interferon signaling supports macrophages role in cytokine release syndrome. We propose vascular immune organoids are a useful platform to model and discover factors that ameliorate SARS-CoV-2-mediated cytokine release syndrome.
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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/10.1101/2024.03.20.585837v1" target="_blank">SARS-CoV-2 infection activates inflammatory macrophages in vascular immune organoids</a>
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</div></li>
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<li><strong>Deep learning of antibody epitopes using molecular permutation vectors</strong> -
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<div>
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The accurate computational prediction of B cell epitopes can vastly reduce the cost and time required for identifying potential epitope candidates for the design of vaccines and immunodiagnostics. However, current computational tools for B cell epitope prediction perform poorly and are not fit-for-purpose, and there remains enormous room for improvement and the need for superior prediction strategies. Here we propose a novel approach that improves B cell epitope prediction by encoding epitopes as binary molecular permutation vectors that represent the position and structural properties of the amino acids within a protein antigen sequence that interact with an antibody, rather than the traditional approach of defining epitopes as scores per amino acid on a protein sequence that pertain to their probability of partaking in a B cell epitope antibody interaction. In addition to defining epitopes as a binary molecular permutation vectors, the approach also uses the 3D macrostructure features of the unbound 3D protein structures, and in turn uses these features to train another deep learning model on the corresponding antibody-bound protein 3D structures. We demonstrate that the strategy predicts B cell epitopes with improved accuracy compared to the existing tools, and reliably identifies the majority of experimentally verified epitopes on the spike protein of SARS-CoV-2 not seen by the model in training. With the approach described herein, a primary protein sequence with the query molecular permutation vector alone is required to predict B cell epitopes in a reliable manner, potentially advancing the use of computational prediction of B cell epitopes in biomedical research applications.
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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/10.1101/2024.03.20.585661v1" target="_blank">Deep learning of antibody epitopes using molecular permutation vectors</a>
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</div></li>
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<li><strong>Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens</strong> -
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<div>
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The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2s usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimers opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.
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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/10.1101/2023.10.24.563841v3" target="_blank">Simulation-Driven Design of Stabilized SARS-CoV-2 Spike S2 Immunogens</a>
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</div></li>
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<li><strong>Identifying causal role of COVID-19 in immunopsychiatry models</strong> -
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<div>
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This preprint is a 1000-word Viewpoint that explores methodological considerations of the COVID-19 pandemic for immunopsychiatry. It has been accepted for publication in Brain, Behavior, and Immunity for a special issue on Immunopsychiatry and COVID-19. Specifically, we discuss the treatment of COVID-19 as a confounding versus mediating variable in immunopsychiatric research. We leverage simulated data varied in sample and effect size to illustrate key considerations. Further, we highlight the statistical implications of each of these scenarios. Recommendations and key considerations for the field are briefly 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/w4d5u/" target="_blank">Identifying causal role of COVID-19 in immunopsychiatry models</a>
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</div></li>
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<li><strong>The advent of the COVID-19 epidemic did not affect Americans’ endorsement of moral foundations</strong> -
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<div>
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Prior work has suggested that existential threats in the form of terror attacks may shift liberals’ reliance on moral foundations to more resemble those of conservatives. We therefore hypothesized that endorsement of these moral foundations would have increased when the COVID-19 epidemic became a salient threat. To examine this hypothesis we conducted a longitudinal study with 237 American participants across the liberal-conservative spectrum, in which their endorsement of various moral foundations were measured before and after the advent of the pandemic. We did not find evidence of any systematic change in the endorsement of any moral foundation, neither in general nor specifically among liberals or specifically among those who perceived the greatest threat from COVID-19. We conclude that the threat from the pandemic does not seem to have had any substantial effect on the moral foundations that people rely on. This finding is consistent with other longitudinal studies of the effect of the COVID-19 pandemic on measures related to conservatism.
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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/957zk/" target="_blank">The advent of the COVID-19 epidemic did not affect Americans’ endorsement of moral foundations</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>Reducing Chronic Breathlessness in Adults by Following a Self-guided, Internet Based Supportive Intervention (SELF-BREATHE)</strong> - <b>Conditions</b>: Advanced Respiratory Disease; Chronic Breathlessness Due to Advanced Respiratory Disease; Chronic Obstructive Pulmonary Disease; Bronchiectasis; Interstitial Lung Disease; Lung Cancer; Asthma; Chronic Fibrotic Lung Disease Following SARS-CoV2 Infection <br/><b>Interventions</b>: Other: SELF-BREATHE <br/><b>Sponsors</b>: King’s College Hospital NHS Trust <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>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SVF for Treating Pulmonary Fibrosis Post COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis <br/><b>Interventions</b>: Biological: Autologous adipose-derived SVF IV administration <br/><b>Sponsors</b>: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua <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>RECOVER-AUTONOMIC Platform Protocol</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)</strong> - <b>Conditions</b>: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>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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<li><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Unusual NiNi interaction in Ni(ii) complexes as potential inhibitors for the development of new anti-SARS-CoV-2 Omicron drugs</strong> - Two nickel(ii) coordination complexes <a href="2">Ni(L)</a>(1) and <a href="n">Ni(L)</a>(2) of a tetradentate Schiff base ligand (H(2)L) derived from 2-hydroxy-1-naphthaldehyde with ethylenediamine were synthesized, designed, and characterized via spectroscopic and single crystal XRD analyses. Both nickel(ii) complexes exhibited unusual Ni⋯Ni interactions and were fully characterized via single-crystal X-ray crystallography. Nickel(ii) complexes <a href="2">Ni(L)</a>(1) and <a href="n">Ni(L)</a>(2) crystallize in monoclinic and triclinic…</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>Integrating virtual screening, pharmacoinformatics profiling, and molecular dynamics: identification of promising inhibitors targeting 3CLpro of SARS-CoV-2</strong> - Introduction: The pursuit of effective therapeutic solutions for SARS-CoV-2 infections and COVID-19 necessitates the repurposing of existing compounds. This study focuses on the detailed examination of the central protease, 3-chymotrypsin-like protease (3CLpro), a pivotal player in virus replication. The combined approach of molecular dynamics simulations and virtual screening is employed to identify potential inhibitors targeting 3CLpro. Methods: A comprehensive virtual screening of 7120…</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>TRIM6 facilitates SARS-CoV-2 proliferation by catalyzing the K29-typed ubiquitination of NP to enhance the ability to bind viral genomes</strong> - The Nucleocapsid Protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not only the core structural protein required for viral packaging, but also participates in the regulation of viral replication, and its post-translational modifications such as phosphorylation have been shown to be an important strategy for regulating virus proliferation. Our previous work identified NP could be ubiquitinated, as confirmed by two independent studies. But the function of NP…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality</strong> - The dysregulated immune response and inflammation resulting in severe COVID-19 are still incompletely understood. Having recently determined that aberrant death-ligand-induced cell death can cause lethal inflammation, we hypothesized that this process might also cause or contribute to inflammatory disease and lung failure following SARS-CoV-2 infection. To test this hypothesis, we developed a novel mouse-adapted SARS-CoV-2 model (MA20) that recapitulates key pathological features of COVID-19….</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>No immunological interference or concerns about safety when seasonal quadrivalent influenza vaccine is co-administered with a COVID-19 mRNA-1273 booster vaccine in adults: A randomized trial</strong> - The objective of the study was to assess the safety and immunogenicity of mRNA-1273 COVID-19 booster vaccination when co-administered with an egg-based standard dose seasonal quadrivalent influenza vaccine (QIV). This was a phase 3, randomized, open-label study. Eligible adults aged ≥ 18 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and QIV 2 weeks apart (Seq group) or concomitantly (Coad group). Primary objectives were non-inferiority of haemagglutinin…</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>Targeted degradation of zDHHC-PATs decreases substrate S-palmitoylation</strong> - Reversible S-palmitoylation of protein cysteines, catalysed by a family of integral membrane zDHHC-motif containing palmitoyl acyl transferases (zDHHC-PATs), controls the localisation, activity, and interactions of numerous integral and peripheral membrane proteins. There are compelling reasons to want to inhibit the activity of individual zDHHC-PATs in both the laboratory and the clinic, but the specificity of existing tools is poor. Given the extensive conservation of the zDHHC-PAT active…</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>Inhibitory effects of senkyuchachosan on SARS-CoV-2 papain-like protease activity in vitro</strong> - Papain-like protease (PLpro) enzyme plays a vital role in viral replication as it breaks down polyproteins and disrupts the host’s immune response. There are few reports on Kampo formulas that focus on PLpro activity. In this study, we evaluated the inhibitory effects of senkyuchachosan, a traditional Japanese medicine, on PLpro of SARS-CoV-2, the virus responsible for causing COVID-19. We purified the PLpro enzyme and conducted in vitro enzymatic assays using specific substrates. Among the nine…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of inositol monophosphatase as a broad-spectrum antiviral target of ivermectin</strong> - Ivermectin has broad-spectrum antiviral activities. Despite the failure in clinical application of COVID-19, it can serve as a lead compound for the development of more effective broad-spectrum antivirals, for which a better understanding of its antiviral mechanisms is essential. We thus searched for potential novel targets of ivermectin in host cells by label-free thermal proteomic profiling using Huh-7 cells. Inositol monophosphatase (IMPase) was found among the proteins with shifted thermal…</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>Optimized Recombinant Expression and Purification of the SARS-CoV-2 Polymerase Complex</strong> - An optimized protocol has been developed to express and purify the core RNA-dependent RNA polymerase (RdRP) complex from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The expression and purification of active core SARS-CoV-2 RdRp complex is challenging due to the complex multidomain fold of nsp12, and the assembly of the multimeric complex involving nsp7, nsp8, and nsp12. Our approach adapts a previously published method to express the core SARS-CoV-2 RdRP complex in…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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