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169 lines
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<title>09 December, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Distance to Vaccine Sites is Associated with Lower COVID-19 Vaccine Uptake</strong> -
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COVID-19 remains a leading cause of mortality in the U.S., despite widespread availability of vaccines. Conventional wisdom ties failure to vaccinate primarily to vaccine-skeptic beliefs (e.g., conspiracy theories, partisanship). Yet in this research, we find that vaccination is also hindered by travel distance to vaccine sites (a form of friction, or structural barriers). In study 1, Californians living farther from vaccine sites had lower vaccination rates, and this effect held regardless of partisanship. In study 2, Chicago zip codes saw an uptick in vaccination following vaccine site opening. These results proved robust in multiverse analyses accounting for a wide range of covariates, outcomes, and distance indicators. COVID-19 vaccination is hampered not just by vaccine hesitancy, but also structural barriers like distance. Efforts to boost vaccination could benefit from minimizing friction.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/mux5s/" target="_blank">Distance to Vaccine Sites is Associated with Lower COVID-19 Vaccine Uptake</a>
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<li><strong>SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized COVID-19 patients</strong> -
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Coronavirus disease 2019 (COVID-19) and associated severity has been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host-microbe homeostasis and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and the COVID-19 patients who had survived or unfortunately died by the end of study enrollment, and between severe disease and healthy controls, as well as performed a correlation analysis between plasma variables and bacterial abundances. The rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including Faecalibacterium prausnitsii, and an increased abundance of the opportunistic pathogens Eggerthella lenta and Hungatella hathewayi. Furthermore, the oral pathogen Scardovia wiggsiae was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both H. hathewayi and S. wiggsiae correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity, and providing potential therapeutic targets for managing COVID-19.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.07.570670v1" target="_blank">SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized COVID-19 patients</a>
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<li><strong>Effects of remote work on population distribution across cities: US evidence from a QSE model</strong> -
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This study investigates the impact of remote work adoption on the size and competitiveness of cities in the United States. As a contribution to the ongoing debate sparked by the Covid-19 pandemic, the research initially establishes city-specific upper-bound measures of potential remote work adoption, utilizing the share of employment in remotely-performable occupations for each city. Subsequently, it employs a Quantitative Spatial Economic model, incorporating shipping and commuting costs, to assess the counterfactual effects that these potential levels of remote work adoption would have on population distribution across US cities. Model predictions indicate that upon full remote-work adoption, only select highly productive cities would grow in size and productivity, tothe detriment of the majority of locations. Nevertheless, the emerging spatial equilibrium yields generalized welfare gains characterized by reduced markups in larger cities, extending even to shrinking cities through the pro-competitive effect of trade. The findings suggest a policy-relevant dual role of remote work, concurrently enhancing welfare while reinforcing agglomeration and inequality across cities.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/krnzq/" target="_blank">Effects of remote work on population distribution across cities: US evidence from a QSE model</a>
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<li><strong>Prediction of mental well-being from individual characteristics and circumstances during the COVID-19 pandemic</strong> -
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The “Mental Health Impact of COVID-19 Pandemic on NIMH Patients and Volunteers” study was a longitudinal study launched in spring 2020 by researchers at NIMH, to investigate the effect of the emerging COVID-19 pandemic on mental health. For each participant, the study collected personal characteristics, such as demographics, psychological traits, and clinical history, together with personal circumstances at regular intervals during their enrollment in the study. In this paper, we examine the degree to which a variety of mental health outcomes over time for an individual can be predicted from personal characteristics and their changing circumstances, using regression models trained on other study participants. We find that it is possible to predict the variation of a participant’s mental health outcomes from time point to time point, for most of the outcomes we consider. This capability is dominated by information about the primary outcome measures that were collected at the time of study enrollment but can be improved by considering personal characteristics and circumstances.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/7enqw/" target="_blank">Prediction of mental well-being from individual characteristics and circumstances during the COVID-19 pandemic</a>
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<li><strong>Verification Theatre at Borders and in Pockets</strong> -
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To appear in: Colleen M. Flood, Y.Y. Brandon Chen, Raywat Deonandan, Sam Halabi, and Sophie Thériault (eds.) Pandemics, Public Health, and the Regulation of Borders: Lessons from COVID-19 (Routledge, forthcoming). This version: August 2023. Abstract The COVID-19 pandemic saw the creation of a wide array of digital infrastructures, underpinning both digital and paper systems, for proving attributes such as vaccination, test results or recovery. These systems were hotly debated. Yet this debate often failed to connect their social, technical and legal aspects, focussing on one area to the exclusion of the others. In this paper, I seek to bring them together. I argue that fraud-free “vaccination certificate” systems were a technical and social pipe-dream, but one that was primarily advantageous to organisations wishing to establish and own infrastructure for future ambitions as verification platforms. Furthermore, attempts to include features to ostensibly reduce fraud had, and risks further, broader knock-on effects on local digital infrastructures around the world, particularly in countries with low IT capacities easily captured by large firms and de facto excluded from and by global standardisation processes. The paper further reflects on the role of privacy in these debates, and how privacy, and more specifically confidentiality, was misconstrued as a main design aim of these systems, when the main social problems could manifest even in a system built with state of the art privacy-enhancing technologies. The COVID-19 pandemic should sharpen our senses towards the importance of infrastructures, and more broadly, how to use technologies in societies in crises.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/h24uv/" target="_blank">Verification Theatre at Borders and in Pockets</a>
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<li><strong>Biosafety, Biosecurity, and Bioethics</strong> -
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The COVID-19 pandemic has highlighted the importance of biosafety in the biomedical sciences. While it is often assumed that biosafety is purely technical matter that has little to do with philosophy or the humanities, biosafety raises important ethical issues that have not been adequately examined in the scientific or bioethics literature. This article reviews some pivotal events in the history of biosafety and biosecurity and explores three different biosafety topics that generate significant ethical concerns, i.e., risk assessment, risk management, and risk distribution. The article also discusses the role of democratic governance in the oversight of biosafety and offers some suggestions for incorporating bioethics into biosafety practice, education, and policy.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/cjf2u/" target="_blank">Biosafety, Biosecurity, and Bioethics</a>
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<li><strong>COVID-19 Lockdowns and Children’s Access to Justice: An Interrupted Time Series Analysis of Moroccan Family court filings</strong> -
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The COVID-19 is a social disaster that has affected the operation of judicial systems globally. Access to justice is a vital right that ensures all other rights can be upheld. This study investigates how national lockdown affected the operation of family courts and children’s access to justice in Morocco. National lockdowns were enforced between March 21th and June 10th 2020 in response to the spread of coronavirus. The general closure of civil society was not extended to the judicial system and family courts were expected to continue operating and provide access to protection and justice. How well the court system mentioned to function under the constraints of stay-at-home orders is an open question. To investigate the impact of the national COVID-19 lockdown on family court systems and access to justice for children in Morocco this study used publicly available court filings (N= 77,335) pertaining to child abuse and neglect from 1st January 2020 to 30th December 2020 spanning the pre-lockdown, lockdown, and post-lockdown periods. Interrupted time series analysis was conducted to assess the impact of the COVID-19 lockdown on court filing outcomes across different case types including penal, civil, complaints, and reports at the national, regional, and court level, controlling for time trends and regional fixed effects. National lockdowns were associated with decrease in cases filed and an increase in the percentages of cases with delays. Average case length differed by case type. Post-lockdown, case numbers recovered however there was large weekly variation likely due to rolling regional lockdowns. Evidence suggests that national lockdowns had a significant adverse impact on the judicial systems ability to provide access to justice for children.
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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/bf8vt/" target="_blank">COVID-19 Lockdowns and Children’s Access to Justice: An Interrupted Time Series Analysis of Moroccan Family court filings</a>
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<li><strong>From Viral Infections to Alzheimer’s Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics</strong> -
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Emerging evidence suggests that certain microorganisms, including viral infections, may contribute to the onset and/or progression of Alzheimer's Disease (AD), a neurodegenerative condition characterized by memory impairment and cognitive decline. However, the precise extent of their involvement and the underlying mechanisms through which specific viruses increase AD susceptibility risk remain elusive. We used an integrative systems bioinformatics approach to identity viral-mediated pathogenic mechanisms by which specific viral species, namely Herpes Simplex Virus 1 (HSV-1), Human Cytomegalovirus (HCMV), Epstein-Barr Virus (EBV), Kaposi Sarcoma-associated Herpesvirus (KSHV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Influenza A virus (IAV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), could facilitate the pathogenesis of AD via virus-host protein-protein interactions (PPIs). We also sought to uncover potential synergistic pathogenic effects resulting from the reactivation of specific herpesviruses (HSV-1, HCMV and EBV) during acute SARS-CoV-2 infection, potentially increasing AD susceptibility. Our findings show that Herpesviridae Family members (HSV-1, EBV, KSHV, HCMV) impact AD-related processes like amyloid-beta formation, neuronal death, and autophagy. Hepatitis viruses (HBV, HCV) influence processes crucial for cellular homeostasis and dysfunction. Importantly, hepatitis viruses affect microglia activation via virus-host PPIs. Reactivation of HCMV during SARS-CoV-2 infection could potentially foster a lethal interplay of neurodegeneration, via synergistic pathogenic effects on AD-related processes like response to unfolded protein, regulation of autophagy, response to oxidative stress and amyloid-beta formation. Collectively, these findings underscore the complex link between viral infections and AD development. Perturbations in AD-related processes by viruses can arise from both shared and distinct mechanisms among viral species in different categories, potentially influencing variations in AD susceptibility.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.05.570187v1" target="_blank">From Viral Infections to Alzheimer’s Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics</a>
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<li><strong>In Silico Therapeutic Intervention on Cytokine Storm in COVID-19</strong> -
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The recent global COVID-19 outbreak, attributed by the World Health Organization to the rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), underscores the need for an extensive exploration of virological intricacies, fundamental pathophysiology, and immune responses. This investigation is vital to unearth potential therapeutic avenues and preventive strategies. Our study delves into the intricate interaction between SARS-CoV-2 and the immune system, coupled with exploring therapeutic interventions to counteract dysfunctional immune responses like the 'cytokine storm' (CS), a driver of disease progression. Understanding these immunological dimensions informs the design of precise multiepitope-targeted peptide vaccines using advanced immunoinformatics and equips us with tools to confront the cytokine storm. Employing a control theory-based approach, we scrutinize the perturbed behavior of key proteins associated with cytokine storm during COVID-19 infection. Our findings support ACE2 activation as a potential drug target for CS control and confirm AT1R inhibition as an alternative strategy. Leveraging deep learning, we identify potential drugs to individually target ACE2 and AT1R, with Lomefloxacin and Fostamatinib emerging as standout options due to their close interaction with ACE2. Their stability within the protein-drug complex suggests superior efficacy among many drugs from our deep-learning analysis. Moreover, there is a significant scope for optimization in fine-tuning protein-drug interactions. Strong binding alone may not be the sole determining factor for potential drugs; precise adjustments are essential. The application of advanced computational power offers novel solutions, circumventing time-consuming lab work. In scenarios necessitating both ACE2 and AT1R targeting, optimal drug combinations can be derived from our analysis of drug-drug interactions, as detailed in the manuscript.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.05.570280v1" target="_blank">In Silico Therapeutic Intervention on Cytokine Storm in COVID-19</a>
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<li><strong>COVID-19-related conspiracy beliefs and their relationship with perceived stress and pre-existing conspiracy beliefs in a Prolific Academic sample: A replication and extension of Georgiou et al. (2020)</strong> -
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The authors reanalyzed the data and conducted a close replication of a study by Georgiou et al. (2020), who found amongst 660 (reported in abstract) or 640 (reported in participant section) participants that 1) COVID-19 related conspiracy theory beliefs were strongly related to broader conspiracy theory beliefs, that 2) COVID-19 related conspiracy beliefs were higher in those with lower levels of education, and that 3) COVID-19 related conspiracy beliefs were positively (although weakly) correlated with more negative attitudes towards different individual items measuring the government’s response. Finally, Georgiou et al. (2020) found that 4) COVID-19 beliefs were unrelated to self-reported stress. Reanalyzing their data and adjusting the analytical framework, the authors only found that an average of attitudes towards the appropriateness of the government response towards the pandemic was negatively related to conspiracy beliefs in general (not just COVID-19). In the present replication and extension study, random forest analyses show that attitude towards government responses (like the original study), stress (unlike the original study), and attachment avoidance towards the partner (unlike the original study) are the most important predictors of conspiracy beliefs. However, the explained variance of the whole random forest model (3.5-7.5%) was low and model fit of the presently and widely used conspiracy belief inventories was poor. Measurement error is a likely explanation for the differences between the original and replication study and independent development-validation studies therefore need to be conducted to better measure conspiracy beliefs.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/t62s7/" target="_blank">COVID-19-related conspiracy beliefs and their relationship with perceived stress and pre-existing conspiracy beliefs in a Prolific Academic sample: A replication and extension of Georgiou et al. (2020)</a>
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<li><strong>Algorithm for selecting potential SARS-CoV-2 dominant variants based on POS-NT frequency</strong> -
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COVID-19, currently prevalent worldwide, is caused by a novel coronavirus, SARS-CoV-2. Similar to other RNA viruses, SARS-CoV-2 continues to evolve through random mutations, creating numerous variants, such as Alpha, Beta, and Delta. It is, therefore, necessary to predict the mutations constituting the dominant variant before they are generated. This can be achieved by continuously monitoring the mutation trends and patterns. Hence, in the current study, we sought to design a dominant variant candidate (DVC) selection algorithm. To this end, we obtained COVID-19 sequence data from GISAID and extracted position-nucleotide (POS-NT) frequency ratio data by country and date through data preprocessing. We then defined the dominant dates for each variant in the USA and developed a frequency ratio prediction model for each POS-NT. Based on this model, we applied DVC criteria to develop the selection algorithm, verified for Delta and Omicron. Using Condition 3 as the DVC criterion, 69 and 102 DVC POS-NTs were identified for Delta and Omicron an average of 47 and 82 days before the dominant dates, respectively. Moreover, 13 and 44 Delta- and Omicron-defining POS-NTs were recognized 18 and 25 days before the dominant dates, respectively. We identified all DVC POS-NTs before the dominant dates, including soaring and gently increasing POS-NTs. Considering that we successfully defined all POS-NT mutations for Delta and Omicron, the DVC algorithm may represent a valuable tool for providing early predictions regarding future variants, helping improve global health.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.05.570216v1" target="_blank">Algorithm for selecting potential SARS-CoV-2 dominant variants based on POS-NT frequency</a>
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<li><strong>Harmonizing Government Responses to the COVID-19 Pandemic</strong> -
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Public health and safety measures (PHSM) made in response to the COVID-19 pandemic have been singular, rapid, and profuse compared to the content, speed, and volume of normal policy-making. Not only can they have a profound effect on the spread of the virus, but they may also have multitudinous secondary effects, in both the social and natural worlds. Unfortunately, despite the best efforts by numerous research groups, existing data on COVID-19 PHSM only partially captures their full geographical scale and policy scope for any significant duration of time. This paper introduces our effort to harmonize data from the eight largest such efforts for policies made before September 21, 2021 into the taxonomy developed by the CoronaNet Research Project in order to respond to the need for comprehensive, high quality COVID-19 data. In doing so, we present a comprehensive comparative analysis of existing data from different COVID-19 PHSM datasets, introduce our novel methodology for harmonizing COVID-19 PHSM data, and provide a clear-eyed assessment of the pros and cons of our efforts.
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🖺 Full Text HTML: <a href="https://osf.io/zb6yx/" target="_blank">Harmonizing Government Responses to the COVID-19 Pandemic</a>
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<li><strong>SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2</strong> -
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SARS-CoV-2 interferes with antigen presentation by downregulating MHC II on antigen presenting cells, but the mechanism mediating this process is unelucidated. Herein, analysis of protein and gene expression in human antigen presenting cells reveals that MHC II is downregulated by the SARS-CoV-2 main protease, NSP5. This suppression of MHC II expression occurs via decreased expression of the MHC II regulatory protein CIITA. This downregulation of CIITA is independent of NSP5’s proteolytic activity, but rather, NSP5 delivers HDAC2 to IRF3 at an IRF binding site within the CIITA promoter. Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a mechanism by which SARS-CoV-2 limits MHC II expression, thereby delaying or weakening the subsequent adaptive immune response. Importance: SARS-CoV-2 alters the expression of many immunoregulatory proteins to limit and delay the host antiviral response, thereby producing a more severe and longer-lasting infection. Preventing and limiting the activation of helper T cells by reducing MHC II expression on antigen presenting cells is one of these strategies, but while this mechanism was identified early in the pandemic, the mechanism allowing SARS-CoV-2 to limit MHC II expression has remained unclear. Herein, we demonstrate that this occurs via a tripartite interaction between viral NSP5 and host HDAC2 and IRF3, where a complex of NSP5 and HDAC2 is recruited to IRF3 bound to the promoter of CIITA - the master regulator of MHC II expression - with the delivery of HDAC2 then mediating the deacetylation of the CIITA promoter and the suppression of MHC II expression.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528032v3" target="_blank">SARS-CoV-2 NSP5 Antagonizes MHC II Expression by Subverting Histone Deacetylase 2</a>
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<li><strong>Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation</strong> -
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In the realm of antibody therapeutics development, increasing the binding affinity of an antibody to its target antigen is a crucial task. This paper presents GearBind, a pretrainable deep neural network designed to be effective for in silico affinity maturation. Leveraging multi-level geometric message passing alongside contrastive pretraining on protein structural data, GearBind capably models the complex interplay of atom-level interactions within protein complexes, surpassing previous state-of-the-art approaches on SKEMPI v2 in terms of Pearson correlation, mean absolute error (MAE) and root mean square error (RMSE). In silico experiments elucidate that pretraining helps GearBind become sensitive to mutation-induced binding affinity changes and reflective of amino acid substitution tendency. Using an ensemble model based on pretrained GearBind, we successfully optimize the affinity of CR3022 to the spike (S) protein of the SARS-CoV-2 Omicron strain. Our strategy yields a high success rate with up to 17-fold affinity increase. GearBind proves to be an effective tool in narrowing the search space for in vitro antibody affinity maturation, underscoring the utility of geometric deep learning and adept pre-training in macromolecule interaction modeling.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.08.10.552845v2" target="_blank">Pretrainable Geometric Graph Neural Network for Antibody Affinity Maturation</a>
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<li><strong>Ribosomal frameshifting and misreading of mRNA in COVID-19 vaccines produces “off-target” proteins and immune responses eliciting safety concerns: Comment on UK study by Mulroney et al.</strong> -
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We comment on the study by Mulroney et al.(1) entitled: “N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting.” The study found evidence in mice and humans for the misreading of the modRNA contained within the Pfizer COVID-19 vaccine to inadvertently produce “off-target” proteins capable of eliciting “off-target” immune responses. The authors propose that these novel proteins are the result of ribosomal frameshifting occasioned by the substitution of N1-methyl pseudouridine. The authors state that the “error prone” code is a safety concern with a “huge potential to be harmful” and that “it is essential that these therapeutics are designed to be free from unintended side-effects.” The findings reveal a developmental and regulatory failure to ask fundamental questions that could affect the safety and effectiveness of these products. According to WHO guidelines for mRNA vaccines, (2) manufacturers should provide details of “unexpected ORFs”(Open Reading Frames). The formation of these off-target proteins is not disclosed in the package insert for COMIRNATY. The finding that unintended proteins may be produced as a result of vaccination is sufficient cause for regulators to conduct full risk assessments of past or future harms that may have ensued. Given that this study was conducted under the auspices of the United Kingdom Government, we must assume UK regulators, manufacturers, and international regulatory agencies, including FDA, were apprised of the data many months ago. We await their account of what steps they have taken to investigate why the formation of off-target proteins was not discovered sooner, what toxic effects they may have caused and what steps they are taken to prevent harm in the future and to inform the public of these findings.
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🖺 Full Text HTML: <a href="https://osf.io/nt8jh/" target="_blank">Ribosomal frameshifting and misreading of mRNA in COVID-19 vaccines produces “off-target” proteins and immune responses eliciting safety concerns: Comment on UK study by Mulroney et al.</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID</strong> - <b>Conditions</b>: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19 <br/><b>Interventions</b>: Drug: Ensitrelvir; Other: Placebo <br/><b>Sponsors</b>: Timothy Henrich; Shionogi Inc. <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>Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Procedure: muscle strengthening <br/><b>Sponsors</b>: Centro Universitário Augusto Motta <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>Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: Immunoglobulins <br/><b>Sponsors</b>: Jaehoon Ko <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Inhaled Hydroxy Gas on Long COVID Symptoms</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Device: Hydroxy gas <br/><b>Sponsors</b>: Oxford Brookes University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question <br/><b>Sponsors</b>: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Community Care Intervention to Decrease COVID-19 Vaccination Inequities</strong> - <b>Conditions</b>: COVID-19 Vaccination <br/><b>Interventions</b>: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB) <br/><b>Sponsors</b>: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD) <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program for PASC Program to Improve Functioning of Persons Suffering From Post-COVID Syndrome: A Randomized Controlled Trial</strong> - <b>Conditions</b>: Post-Acute COVID-19; Post-Acute COVID-19 Syndrome; Post-Acute COVID-19 Infection; Long COVID; Long Covid19; Dyspnea; Orthostasis; Cognitive Impairment <br/><b>Interventions</b>: Other: Comprehensive Rehabilitation; Other: Augmented Usual Care <br/><b>Sponsors</b>: University of Pennsylvania; Medical College of Wisconsin; National Institutes of Health (NIH) <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>Stem Cell Study for Long COVID-19 Neurological Symptoms</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Biological: Stem Cell <br/><b>Sponsors</b>: Charles Cox; CBR Systems, Inc. <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>Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial</strong> - <b>Conditions</b>: Long-COVID; Long Covid19; Post-COVID-19 Syndrome; Post-COVID Syndrome; Fatigue <br/><b>Interventions</b>: Other: COVIDEx <br/><b>Sponsors</b>: Lawson Health Research Institute; Western University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Multilevel Intervention <br/><b>Sponsors</b>: San Diego State University <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Drug: Metformin; Other: Placebo <br/><b>Sponsors</b>: Trust for Vaccines and Immunization, Pakistan <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized Trial Evaluating a mRNA VLP Vaccine’s Immunogenicity and Safety for COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: AZD9838; Biological: Licensed mRNA vaccine <br/><b>Sponsors</b>: AstraZeneca <br/><b>Not yet recruiting</b></p></li>
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</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>New anti-SARS-CoV-2 aminoadamantane compounds as antiviral candidates for the treatment of COVID-19</strong> - Here, the antiviral activity of aminoadamantane derivatives were evaluated against SARS-CoV-2. The compounds exhibited low cytotoxicity to Vero, HEK293 and CALU-3 cells up to a concentration of 1,000 µM. The inhibitory concentration (IC(50)) of aminoadamantane was 39.71 µM in Vero CCL-81 cells and the derivatives showed significantly lower IC(50) values, especially for compounds 3F4 (0.32 µM), 3F5 (0.44 µM) and 3E10 (1.28 µM). Additionally, derivatives 3F5 and 3E10 statistically reduced the…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pan-antiviral effects of a PIKfyve inhibitor on respiratory virus infection in human nasal epithelium and mice</strong> - Endocytosis, or internalization through endosomes, is a major cell entry mechanism used by respiratory viruses. Phosphoinositide 5-kinase (PIKfyve) is a critical enzyme for the synthesis of phosphatidylinositol (3, 5)biphosphate (PtdIns (3, 5)P2) and has been implicated in virus trafficking via the endocytic pathway. In fact, antiviral effects of PIKfyve inhibitors against SARS-CoV-2 and Ebola have been reported, but there is little evidence regarding other respiratory viruses. In this study, we…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Analysis of bioactive compounds of <em>Olea europaea</em> as potential inhibitors of SARS-CoV-2 main protease: a pharmacokinetics, molecular docking and molecular dynamics simulation studies</strong> - COVID-19 is a highly infectious disease caused by a new type of extremely contagious coronavirus called SARS-CoV-2. The virus’s main protease enzyme, SARS-CoV-2 Mpro, is essential for its replication and transcription processes. Targeting this enzyme presents a promising avenue for antiviral drug development. Researchers have explored the intricate three-dimensional configurations of the enzyme, analyzing its interactions with various inhibitors. These findings provide a foundation for designing…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Design, synthesis and biological evaluation of biaryl amide derivatives against SARS-CoV-2 with dual-target mechanism</strong> - The COVID-19 pandemic highlights the urgent need to develop effective small-molecule antivirals. Thirty-three novel biaryl amide derivatives were synthesized and evaluated for anti-coronaviral activity. Some significant SARs were uncovered and the intensive structure modifications led to the most active compounds 8b and 8h. The broad-spectrum anti-coronaviral effects of 8h were validated at RNA and protein levels. 8h inhibits coronavirus replication at multiple stages, from virus entry to virus…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 infection and replication by Petasites hybridus CO2-extract (Ze 339)</strong> - CONCLUSION: Thereby, Ze 339 attenuated epithelial infection by SARS-CoV-2 and modeled the IFN response. In conclusion, this study highlights Ze 339 as a potential treatment option for COVID-19 that limits infection-associated cell intrinsic immune responses.</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>Integrin α<sub>5</sub>β<sub>1</sub> contributes to cell fusion and inflammation mediated by SARS-CoV-2 spike via RGD-independent interaction</strong> - The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infects host cells by engaging its spike (S) protein with human ACE2 receptor. Recent studies suggest the involvement of integrins in SARS-CoV-2 infection through interaction with the S protein, but the underlying mechanism is not well understood. This study investigated the role of integrin α(5)β(1), which recognizes the Arg-Gly-Asp (RGD) motif in its physiological ligands, in S-mediated virus entry and cell-cell fusion. Our…</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>Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting main protease and papain-like protease</strong> - The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be over, but its variants continue to emerge, and patients with mild symptoms having long COVID is still under investigation. SARS-CoV-2 infection leading to elevated cytokine levels and suppressed immune responses set off cytokine storm, fatal systemic inflammation, tissue damage, and multi-organ failure. Thus, drug molecules targeting the SARS-CoV-2 virus-specific…</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>Strategies to Mitigate the Drug-Drug Interaction between Nirmatrelvir/Ritonavir and Tacrolimus in Allogeneic Hematopoietic Stem Cell Transplant Recipients on Azole Antifungals: Results of a Case Series</strong> - CONCLUSION: NIM/r-tacrolimus is a serious drug-drug interaction which can be mitigated by early discontinuation of tacrolimus and azole antifungals, close monitoring, and reinitiation of tacrolimus and antifungal 48-72 h after completion of therapy.</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>Patterns of physical activity among nursing home residents before and during the Covid 19 pandemic-a systematic observation</strong> - CONCLUSIONS: Nursing homes constitute highly sedentary places-an issue exacerbated by access restrictions for external activity experts and significant others as well as behavioural restrictions for residents during the Covid-19 pandemic. Staff could not compensate due to existing time restraints and lack of training in PA promotion. Based on our findings, we recommend future studies to develop feasible and resource-low activities to be integrated into the daily routines of nursing homes.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A natural product YSK-A blocks SARS-CoV-2 propagation by targeting multiple host genes</strong> - Natural products and herbal medicine have been widely used in drug discovery for treating infectious diseases. Recent outbreak of COVID-19 requires various therapeutic strategies. Here, we used YSK-A, a mixture of three herbal components Boswellia serrata, Commiphora myrrha, and propolis, to evaluate potential antiviral activity against SARS-CoV-2. We showed that YSK-A inhibited SARS-CoV-2 propagation with an IC(50) values of 12.5 µg/ml and 15.42 µg/ml in Vero E6 and Calu-3 cells, respectively….</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>Validation of nuclear receptor RORγ isoform 1 as a novel host-directed antiviral target based on the modulation of cholesterol levels</strong> - Currently, the clinically approved repertoire of antiviral drugs predominantly comprises direct-acting antivirals (DAAs). However, the use of DAAs is frequently limited by adverse effects, restriction to individual virus species, or the induction of viral drug resistance. These issues will likely be resolved by the introduction of host-directed antivirals (HDAs) targeting cellular proteins crucial for viral replication. However, experiences with the development of antiviral HDAs and clinical…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of non-muscular myosin light chain kinase accelerates the clearance of inflammatory cells by promoting the lysosome-mediated cell death</strong> - Infections like COVID-19 are the primary cause of death around the world because they can cause acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and sepsis. Inflammatory cells serve as crucial protective barriers in these diseases. However, excessive accumulation of inflammatory cells is also one of the major causes of organ damage. The non-muscular myosin light chain kinase (nmMLCK) plays crucial of cytoskeletal components involved in endothelial cell-matrix and cell-cell…</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>Crystal structure of SARS-CoV-2 main protease (M<sup>pro</sup>) mutants in complex with the non-covalent inhibitor CCF0058981</strong> - SARS-CoV-2 constantly circulates and evolves worldwide, generating many variants and posing a menace to global health. It is urgently needed to discover effective medicines to treat the disease caused by SARS-CoV-2 and its variants. An established target for anti-SARS-CoV-2 drug discovery is the main protease (M^(pro)), since it exerts an irreplaceable action in viral life cycle. CCF0058981, derived from ML300, is a non-covalent inhibitor that exhibits low nanomolar potency against SARS-CoV-2…</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>USP2 inhibition prevents infection with ACE2-dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice</strong> - Targeting angiotensin-converting enzyme 2 (ACE2) represents a promising and effective approach to combat not only the COVID-19 pandemic but also potential future pandemics arising from coronaviruses that depend on ACE2 for infection. Here, we report ubiquitin specific peptidase 2 (USP2) as a host-directed antiviral target; we further describe the development of MS102, an orally available USP2 inhibitor with viable antiviral activity against ACE2-dependent coronaviruses. Mechanistically, USP2…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Molecular Generative Model of COVID-19 Main Protease Inhibitors Using Long Short-Term Memory-Based Recurrent Neural Network</strong> - The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious threat to public health and prompted researchers to find anti-coronavirus 2019 (COVID-19) compounds. In this study, the long short-term memory-based recurrent neural network was used to generate new inhibitors for the coronavirus. First, the model was trained to generate drug compounds in the form of valid simplified molecular-input line-entry system strings. Then, the structures of COVID-19 main protease…</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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