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<title>18 November, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response</strong> -
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<div>
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Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTD) including Covid19 but there is almost no data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. We used histology and high-dimensional imaging to characterise fatal lung disease in Malawian adults with (n=9) and without (n=7) Covid19, and generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved Covid19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in the Malawi cohort, by response to interferon-gamma in lung-resident alveolar macrophages, in USA, European and Asian cohorts by type I/III interferon responses, particularly in blood-derived monocytes. HIV status had minimal impact on histology or immunopathology. Our study provides data resources and highlights the importance of studying the cellular mechanisms of disease in underrepresented populations, indicating shared and distinct targets for treatment.
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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/10.1101/2023.11.16.566964v1" target="_blank">Spatially resolved single-cell atlas of the lung in fatal Covid19 in an African population reveals a distinct cellular signature and an interferon gamma dominated response</a>
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</div></li>
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<li><strong>Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling.</strong> -
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<div>
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Assessing the impact of SARS-CoV-2 on organelle dynamics allows a better understanding of the mechanisms of viral replication. We combine label-free holo-tomographic microscopy (HTM) with Artificial Intelligence (AI) to visualize and quantify the subcellular changes triggered by SARS-CoV-2 infection. We study the dynamics of shape, position and dry mass of nucleoli, nuclei, lipid droplets (LD) and mitochondria within hundreds of single cells from early infection to syncytia formation and death. SARS-CoV-2 infection enlarges nucleoli, perturbs LD, changes mitochondrial shape and dry mass, and separates LD from mitochondria. We then used Bayesian statistics on organelle dry mass states to define organelle cross-regulation (OCR) networks and report modifications of OCR that are triggered by infection and syncytia formation. Our work highlights the subcellular remodeling induced by SARS-CoV-2 infection and provides a new AI-enhanced, label-free methodology to study in real-time the dynamics of cell populations and their content.
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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/10.1101/2023.11.16.567378v1" target="_blank">Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling.</a>
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</div></li>
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<li><strong>Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers</strong> -
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<div>
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Understanding adaptive immunity against SARS-CoV-2 is a major requisite for the development of effective vaccines and treatments for COVID-19. CD4+ T cells play an integral role in this process primarily by generating antiviral cytokines and providing help to antibody-producing B cells. To empower detailed studies of SARS-CoV-2-specific CD4+ T cell responses in mouse models, we comprehensively mapped I-Ab restricted epitopes for the spike and nucleocapsid proteins of the BA.1 variant of concern via IFN{gamma} ELISpot assay. This was followed by the generation of corresponding peptide:MHCII tetramer reagents to directly stain epitope-specific T cells. Using this rigorous validation strategy, we identified 6 reliably immunogenic epitopes in spike and 3 in nucleocapsid, all of which are conserved in the ancestral Wuhan strain. We also validated a previously identified epitope from Wuhan that is absent in BA.1. These epitopes and tetramers will be invaluable tools for SARS-CoV-2 antigen-specific CD4+ T cell studies in mice.
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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/10.1101/2023.11.16.566918v1" target="_blank">Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers</a>
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</div></li>
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<li><strong>Human microbiota is a reservoir of SARS-CoV-2 advantageous mutations</strong> -
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<div>
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SARS-CoV-2 mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape, are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we show that the human microbiota may contribute to mutations in variants of concern (VOCs). We identified a mutation and adjacent 6 amino acids (aa) in a viral mutation fragment (VMF) and searched for homologous fragments (HFs) in the National Center for Biotechnology Information (NCBI) database. Among the approximate 8000 HFs obtained, 61 mutations in S and other outer membrane proteins were found in bacteria, accounting for 62% of all mutation sources, which is a 12-fold higher than the natural variable proportion. Approximately 70% of these bacterial species belong to the human microbiota, are primarily distributed in the gut or lung and exhibit a composition pattern similar to that of COVID-19 patients. Importantly, SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) replicates corresponding bacterial mRNAs harboring mutations, producing chimeric RNAs. Collectively, SARS-CoV-2 may acquire mutations from the human microbiota, resulting in alterations in the binding sites or antigenic determinants of the original virus. Our study sheds light on the evolving mutational mechanisms of SARS-CoV-2.
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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/10.1101/2023.11.16.567485v1" target="_blank">Human microbiota is a reservoir of SARS-CoV-2 advantageous mutations</a>
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</div></li>
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<li><strong>Krisp: A python package for designing CRISPR and amplification-based diagnostic assays from whole genome data</strong> -
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<div>
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Recent pandemics such as COVID-19 have highlighted the importance of rapidly developing diagnostics to detect and monitor evolving pathogens. CRISPR-Cas technology, combined with isothermal DNA amplification methods, has recently been used to develop diagnostic assays for sequence-specific recognition of DNA or RNA. These assays have similar sensitivity to the gold standard qPCR but can be deployed as easy to use and inexpensive test strips. However, the discovery of diagnostic regions of a genome flanked by conserved regions where primers can be designed requires extensive bioinformatic analyses of genome sequences. We developed the python package krisp to find primers and diagnostic sequences that differentiate groups of samples from each other at any taxonomic scale, using either unaligned genome sequences or a variant call format (VCF) file as input. Krisp has been optimized to handle large datasets by using efficient algorithms that run in near linear time, use minimal RAM, and leverage parallel processing when available. The validity of krisp results has been demonstrated in the laboratory with the successful design of SHERLOCK assays to distinguish the sudden oak death pathogen Phytophthora ramorum from closely related Phytophthora species. Krisp is released open source under a permissive license with all the documentation needed to quickly design CRISPR-Cas diagnostic assays.
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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/10.1101/2023.11.16.567433v1" target="_blank">Krisp: A python package for designing CRISPR and amplification-based diagnostic assays from whole genome data</a>
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</div></li>
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<li><strong>Unveiling the Emotional Turmoil: How Covid-19 impacted researchers and the pursuit of emotional well-being in academia.</strong> -
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<div>
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The Covid-19 crisis unprecedentedly required researchers to adapt to significant changes in their work and personal lives. Our study aims to fill this gap analysing the Covid-19 emotional impact and confinement potential disruptions on researchers activity (specifically, those related to working conditions, caring responsibilities, health, balance, and social support) considering the modulating role played by age, gender, and job position. An online survey was distributed during the first lockdown period of the Covid-19 pandemic, and answers from 1301 researchers (ECR %, senior researchers %) working in Sciences (28.1%), Social Sciences (25.9%), Humanities (16.2%), Health (16.2%) and in Engineering and Architecture (13.5%) were collected. The study highlights that the initial lockdown during the Covid-19 pandemic had a significant emotional impact on researchers, exacerbating pre-existing emotional distress and burnout within this group. Factors such as age, health, gender, and difficulties in balancing work and family life were associated with an increased risk of burnout and emotional distress. Lack of social support was identified as a significant risk factor, while the academic culture prioritizing productivity over well-being contributed to the issue. These findings underscore the need for greater support and cultural changes in academia to preserve researchers' mental health and prevent the chronicization of mental health issues in young academics.
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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/10.1101/2023.11.15.567306v1" target="_blank">Unveiling the Emotional Turmoil: How Covid-19 impacted researchers and the pursuit of emotional well-being in academia.</a>
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</div></li>
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<li><strong>Extending the welcome: a pluralist and coevolutionary analysis of the transformation of induction and transition provision</strong> -
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<div>
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This paper reflects on an institution-wide transformation of student welcome, induction and transition (WIT) at a large, research-intensive UK university, a change accelerated by the Covid-19 pandemic. The paper examines this process of change, from its origins, through its evolution, and co-evolution, over three academic years since the onset of the Pandemic. To do so, the paper adopts a pluralist approach, utilising theories of change established in higher education literature: Kift’s transition pedagogy and Kotter’s model of organisational change. Crucially, it augments these with a co-evolutionary approach examining interacting populations, learning and qualitative change, which may provide useful insights to other institutions navigating changes to WIT provision.
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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/edarxiv/emh3c/" target="_blank">Extending the welcome: a pluralist and coevolutionary analysis of the transformation of induction and transition provision</a>
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</div></li>
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<li><strong>Species and habitat specific changes in bird activity in an urban environment during Covid 19 lockdown</strong> -
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<div>
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Covid-19 lockdowns provided ecologists with a rare opportunity to examine how animals behave when humans are absent. Indeed many studies reported various effects of lockdowns on animal activity, especially in urban areas and other human-dominated habitats. We explored how Covid-19 lockdowns in Israel have influenced bird activity in an urban environment by using continuous acoustic recordings to monitor three common bird species that differ in their level of adaptation to the urban ecosystem: (1) the hooded crow, an urban exploiter, which depends heavily on anthropogenic resources; (2) the rose-ringed parakeet, an invasive alien species that has adapted to exploit human resources; and (3) the graceful prinia, an urban adapter, which is relatively shy of humans and can be found urban habitats with shrubs and prairies. Acoustic recordings provided continuous monitoring of bird activity without an effect of the observer on the animal. We performed dense sampling of a 1.3 square km area in northern Tel-Aviv by placing 17 recorders for more than a month in different micro-habitats within this region including roads, residential areas and urban parks. We monitored both lockdown and no-lockdown periods. We portray a complex dynamic system where the activity of specific bird species depended on many environmental parameters and decreases or increases in a habitat-dependent manner during lockdown. Specifically, urban exploiter species decreased their activity in most urban habitats during lockdown, while human adapter species increased their activity during lockdown especially in parks where humans were absent. Our results also demonstrate the value of different habitats within urban environments for animal activity, specifically highlighting the importance of urban parks. These species- and habitat-specific changes in activity might explain the contradicting results reported by others who have not performed a habitat specific analysis.
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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/10.1101/2023.06.03.543542v3" target="_blank">Species and habitat specific changes in bird activity in an urban environment during Covid 19 lockdown</a>
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</div></li>
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<li><strong>Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting virus-specific enzymes</strong> -
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<div>
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The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus (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 proteins or capable of suppressing the host inflammatory responses to viral infection would provide an effective antiviral therapy against emerging variants of concern. Evolutionarily conserved papain-like protease (PLpro) and main protease (Mpro) play an indispensable role in the virus life cycle and immune evasion. Direct-acting antivirals targeting both these viral proteases represent an attractive antiviral strategy that is also expected to reduce viral inflammation. The present study has evaluated the antiviral and anti-inflammatory potential of natural triterpenoids: azadirachtin, withanolide_A, and isoginkgetin. These molecules inhibit the Mpro and PLpro proteolytic activities with half-maximal inhibitory concentrations (IC50) values ranging from 1.42 to 32.7 M. Isothermal titration calorimetry (ITC) analysis validated the binding of these compounds to Mpro and PLpro. As expected, the two compounds, withanolide_A and azadirachtin exhibit potent anti-SARS-CoV-2 activity in cell-based assays, with half-maximum effective concentration (EC50) values of 21.73 M and 31.19 M, respectively. The anti-inflammatory role of azadirachtin and withanolide_A when assessed using HEK293T cells were found to significantly reduce the levels of CXCL10, TNF, IL6, and IL8 cytokines, which are elevated in severe cases of COVID-19. Interestingly, azadirachtin and withanolide_A were also found to rescue the decreased type-I interferon response (IFN-1). The results of this study clearly highlight the role of triterpenoids as effective antiviral molecules that target SARS-CoV-2 specific enzymes and also host immune pathways involved in virus mediated inflammation.
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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/10.1101/2023.06.24.546363v2" target="_blank">Unraveling antiviral efficacy of multifunctional immunomodulatory triterpenoids against SARS-COV-2 targeting virus-specific enzymes</a>
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</div></li>
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<li><strong>DEFEN-CE: Social Dialogue in Defence of Vulnerable Groupsin Post?COVID-19 Labour Markets. Report on Czechia and Slovakia</strong> -
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<div>
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This report is part of the EC-funded research project DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets (VS/2021/0196). It scrutinizes how social partners influenced COVID-19-related policy responses towards vulnerable groups in the labour market, and whether this experience created opportunities for strengthening social dialogue in general. The empirical focus is on Czechia and Slovakia as representatives of embedded neoliberal countries. This means liberalizing labour market policies during their economic transition starting in the 1990s, but at the same time, anchoring some institutional mechanisms of policy-making, including social dialogue at the national level. The analysis is based on new empirical data in two dimensions: • primary data on policy measures relevant for the vulnerable groups in the labour market, categorized in a standard database of the most important COVID-19 measures relevant for vulnerable groups. • 19 original semi-structured interviews with employer organizations, trade unions, governments, and NGOs in Czechia and Slovakia, implemented in 2022-2023.
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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/cvprx/" target="_blank">DEFEN-CE: Social Dialogue in Defence of Vulnerable Groupsin Post?COVID-19 Labour Markets. Report on Czechia and Slovakia</a>
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</div></li>
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<li><strong>DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Report on Turkey</strong> -
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<div>
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This report is part of an EU-wide project on the social dialogue regarding labour relations during the Covid-19 pandemic. More specifically the report aims to answer the following questions: 1. What public policy and social dialogue measures targeting the selected vulnerable groups were implemented for employment and social protection during the COVID-19 pandemic 2020-2022? 2. To what extent and how did social dialogue play a role in the implementation of social and employment rights of selected vulnerable groups in the COVID-19 pandemic between 2020 and 2022? 3. What lessons and opportunities does the COVID-19 pandemic yield for strengthening social dialogue in the studied countries? In the report, secondary and primary data sources are combined. Labour market and industrial relations analysis largely rely on existing literature. Social policies during the Covid-19 pandemic are based on the Turkish DEFEN-CE Database, which combines multiple sources such as international reports, official documents, reports from trade unions and employers’ organizations, and academic literature. To understand the role of social partners in the defense of vulnerable groups, the report uses 9 semi-structured interviews. 3 Trade Union and 3 Employer Associations from different confederations representing workers and employers across different sectors and sizes are selected to provide a broad range of opinions. Additionally, two NGOs that were quite active during the pandemic and the Turkish Medical Association as one of the most vocal groups and the representative of healthcare sector workers were chosen for interviews. No government officials, either at the local or national level, were willing or able to participate in the interviews. All interviews were analysed using qualitative content analysis based on a DEFEN-CE coding scheme.
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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/d5xea/" target="_blank">DEFEN-CE: Social Dialogue in Defence of Vulnerable Groups in Post-COVID-19 Labour Markets. Report on Turkey</a>
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<li><strong>Evolutionary arms race between SARS-CoV-2 and interferon signaling via dynamic interaction with autophagy.</strong> -
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<div>
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SARS-CoV-2 emerged, and is evolving to efficiently infect humans worldwide. SARS-CoV-2 evades early innate recognition, interferon signaling activated only in bystander cells. This balance of innate activation and viral evasion has important consequences, but the pathways involved are incompletely understood. Here we find that autophagy genes regulate innate immune signaling, impacting the basal set point of interferons, and thus permissivity to infection. Mechanistically, autophagy genes negatively regulate MAVS, and this low basal level of MAVS is efficiently antagonized by SARS-CoV-2 ORF9b, blocking interferon activation in infected cells. However, upon loss of autophagy increased MAVS overcomes ORF9b-mediated antagonism suppressing infection. This has led to the evolution of SARS-CoV-2 variants to express higher levels of ORF9b, allowing SARS-CoV-2 to replicate under conditions of increased MAVS signaling. Altogether, we find a critical role of autophagy in the regulation of innate immunity and uncover an evolutionary trajectory of SARS-CoV-2 ORF9b to overcome host defenses.
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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/10.1101/2023.11.13.566859v1" target="_blank">Evolutionary arms race between SARS-CoV-2 and interferon signaling via dynamic interaction with autophagy.</a>
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</div></li>
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<li><strong>The Impact of SIV-Induced Immunodeficiency on Clinical Manifestation, Immune Response, and Viral Dynamics in SARS-CoV-2 Coinfection</strong> -
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<div>
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Persistent and uncontrolled SARS-CoV-2 replication in immunocompromised individuals has been observed and may be a contributing source of novel viral variants that continue to drive the pandemic. Importantly, the effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. Here we conducted a pilot study wherein two pigtail macaques (PTM) chronically infected with SIVmac239 were exposed to SARS-CoV-2 and monitored for six weeks for clinical disease, viral replication, and viral evolution, and compared to our previously published cohort of SIV-naive PTM infected with SARS-CoV-2. At the time of SARS-CoV-2 infection, one PTM had minimal to no detectable CD4+ T cells in gut, blood, or bronchoalveolar lavage (BAL), while the other PTM harbored a small population of CD4+ T cells in all compartments. Clinical signs were not observed in either PTM; however, the more immunocompromised PTM exhibited a progressive increase in pulmonary infiltrating monocytes throughout SARS-CoV-2 infection. Single-cell RNA sequencing (scRNAseq) of the infiltrating monocytes revealed a less activated/inert phenotype. Neither SIV-infected PTM mounted detectable anti-SARS-CoV-2 T cell responses in blood or BAL, nor anti-SARS-CoV-2 neutralizing antibodies. Interestingly, despite the diminished cellular and humoral immune responses, SARS-CoV-2 viral kinetics and evolution were indistinguishable from SIV-naive PTM in all sampled mucosal sites (nasal, oral, and rectal), with clearance of virus by 3-4 weeks post infection. SIV-induced immunodeficiency significantly impacted immune responses to SARS-CoV-2 but did not alter disease progression, viral kinetics or evolution in the PTM model. SIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral 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/10.1101/2023.11.15.567132v1" target="_blank">The Impact of SIV-Induced Immunodeficiency on Clinical Manifestation, Immune Response, and Viral Dynamics in SARS-CoV-2 Coinfection</a>
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</div></li>
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<li><strong>The SHOW COVID-19 cohort: methods and rationale for examining the statewide impact of COVID-19 on the social determinants of health</strong> -
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Background: National and large city mortality and morbidity data emerged during the early years of the COVID-19 pandemic, yet statewide data to assess the impact COVID-19 had across urban and rural landscapes on subpopulations was lacking. The SHOW COVID-19 cohort was established to provide descriptive and longitudinal data to examine the influence the social determinants of health had on COVID-19 related outcomes. Methods: Participants were recruited from the 5,742 adults in the Survey of the Health of Wisconsin (SHOW) cohort who were all residents of Wisconsin, United States when they joined the cohort between 2008-2019. Online surveys were administered at three timepoints during 2020-2021. Survey topics included COVID-19 exposure, testing and vaccination, COVID-19 impact on economic wellbeing, healthcare access, mental and emotional health, caregiving, diet, lifestyle behaviors, social cohesion, and resilience. Results: A total of 2,304 adults completed at least one COVID-19 online survey, with n=1,090 completing all three survey timepoints. Non-Whites were 2-3 times more likely to report having had COVID-19 compared to Whites, females were more likely than males to experience disruptions in their employment, and those with children in the home were more likely to report moderate to high levels of stress compared to adults without children. Conclusion: Longitudinal, statewide cohorts are important for investigating how the social determinants of health affect health and well-being during the first years of a pandemic and offer insight into future pandemic preparation. The data are available for researchers and cohort is active for continued and future follow-up.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.10.17.23297146v2" target="_blank">The SHOW COVID-19 cohort: methods and rationale for examining the statewide impact of COVID-19 on the social determinants of health</a>
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<li><strong>Becoming A Resilient Scientist Series: An Intervention Program</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Compared to the general population, science trainees experience challenges and heightened stressors that often lead to adverse mental health outcomes. With COVID-19, the stressors of social distancing, isolation, truncated lab time, and uncertainty about the future have all likely exacerbated these issues. Now, more than ever, practical and effective interventions are vitally needed to address the core causes of stress among science trainees and increase their resilience. This paper introduces a new resilience program targeted to biomedical trainees and scientists - Becoming a Resilient Scientist Series (BRS), a multi-part workshop complemented by facilitated group discussions all aimed at bolstering resilience, particularly in the context of academic and research environments. To assess the program9s efficacy, participants completed resilience measures and related assessments before and after completing the series. The results demonstrate that BRS significantly enhances trainee resilience (primary outcome) and reduces perceived stress, anxiety, and work-related presenteeism, as well as increased adaptability, self-awareness, and self-efficacy (secondary outcomes). Furthermore, program participants reported a high level of satisfaction, a strong willingness to recommend the program to others, and perceived positive changes in their resilience skills. To the best of our knowledge, this is the first resilience program designed explicitly for biomedical trainees and scientists, tailored to their unique professional culture and work environment.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.05.02.23289388v4" target="_blank">Becoming A Resilient Scientist Series: An Intervention Program</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial</strong> - <b>Conditions</b>: Long COVID-19 Syndrome; Chronic Fatigue Syndrome <br/><b>Interventions</b>: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet <br/><b>Sponsors</b>: Cardresearch <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ <br/><b>Sponsors</b>: Abbott Rapid Dx <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>Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities</strong> - <b>Conditions</b>: COVID-19; Vaccine <br/><b>Interventions</b>: Behavioral: REDES; Behavioral: Control <br/><b>Sponsors</b>: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers 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>Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes</strong> - <b>Conditions</b>: Normobaric Hypoxia; Hypoventilation; Normoxia <br/><b>Interventions</b>: Other: Repeated sprint <br/><b>Sponsors</b>: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray</strong> - <b>Conditions</b>: SARS-CoV-2; Prevention <br/><b>Interventions</b>: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient <br/><b>Sponsors</b>: The Second Affiliated Hospital of Chongqing Medical 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>Building Engagement Using Financial Incentives Trial - Colorectal Cancer Screening</strong> - <b>Conditions</b>: Health Behavior; Colorectal Cancer; Influenza; COVID-19; Vaccine Hesitancy; Vaccine-Preventable Diseases; Healthcare Patient Acceptance <br/><b>Interventions</b>: Behavioral: Financial incentive for colorectal cancer screening; Behavioral: Financial incentive for flu shot; Behavioral: Financial incentive for COVID-19 shot <br/><b>Sponsors</b>: Tulane University; National Heart, Lung, and Blood Institute (NHLBI) <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel to Support Home Use</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ COVID-19/Flu A&B Panel <br/><b>Sponsors</b>: Abbott Rapid Dx <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>Effects of Rehabilitation Combined With a Maintenance Program Compared to Rehabilitation Alone in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Procedure: Rehabilitation combined to a digital maintenance program; Procedure: Rehabilitation without maintenance program <br/><b>Sponsors</b>: Schön Klinik Berchtesgadener Land; Bavarian State Ministry of Health and Care (Funding); Deutsche Rentenversicherung Bund (German pension insurance) (Design); Betriebskrankenkassen Landesverband Bayern (Bavarian health insurance) (Design) <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>Child and Adolescent Mental Health Literacy for Primary Schools Teachers. A Multicomponent Intervention</strong> - <b>Conditions</b>: Child Mental Health <br/><b>Interventions</b>: Behavioral: Child Mental Health Literacy Program <br/><b>Sponsors</b>: Universidad de Valparaiso <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>Brief Digital Intervention to Increase COVID-19 Vaccination Among Individuals With Anxiety or Depression</strong> - <b>Conditions</b>: Misinformation; Vaccine Hesitancy; Anxiety; Depression; COVID-19 <br/><b>Interventions</b>: Behavioral: Attitudinal inoculation; Behavioral: Cognitive-behavioral therapy-informed intervention; Behavioral: Conventional public health messaging <br/><b>Sponsors</b>: City University of New York, School of Public Health; University of North Carolina, Chapel Hill <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>Type I interferon signaling induces a delayed antiproliferative response in respiratory epithelial cells during SARS-CoV-2 infection</strong> - The proliferation of respiratory epithelial cells is crucial to host recovery from acute lung injury caused by SARS-CoV-2 and other viral pathogens, but the molecular pathways that govern this process are poorly understood. We performed a high-throughput CRISPR screen that surprisingly revealed a detrimental effect of specific host response, type I interferon (IFN-I) signaling, on the fitness of SARS-CoV-2-infected Calu-3 cells. While IFN-I signaling has been previously associated with several…</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>Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses</strong> - The emerging viruses SARS-CoV-2 and arenaviruses cause severe respiratory and hemorrhagic diseases, respectively. The production of infectious particles of both viruses and virus spread in tissues requires cleavage of surface glycoproteins (GPs) by host proprotein convertases (PCs). SARS-CoV-2 and arenaviruses rely on GP cleavage by PCs furin and subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P), respectively. We report improved luciferase-based reporter cell lines, named luminescent…</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 Ebselen derivatives as novel SARS-CoV-2 main protease inhibitors: Design, synthesis, biological evaluation, and structure-activity relationships exploration</strong> - The main protease (M^(pro)) represents one of the most effective and attractive targets for designing anti-SARS-CoV-2 drugs. In this study, we designed and synthesized a novel series of Ebselen derivatives by incorporating privileged fragments from different pockets of the M^(pro) active site. Among these compounds, 11 compounds showed submicromolar activity in the FRET-based SARS-CoV-2 M^(pro) inhibition assay, with IC(50) values ranging from 233 nM to 550 nM. Notably, compound 3a displayed…</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>Traditional Formulations for Managing COVID-19: A Systematic Review</strong> - Background: The advancing etiopathogenesis, diagnosis, and treatment of the global coronavirus disease 2019 (COVID-19) pandemic have prompted the medical community to consider Ayurveda, Siddha, and Unani as add-on preventive and therapeutic options. Objective: To explore the effect of standalone or integrative Traditional Formulations (TFs) on selected clinical symptoms and biomarkers of COVID-19. Search strategy: Out of 465 articles identified from PubMed, ScienceDirect, and Scopus, 17…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential drug-drug interactions of frequently prescribed medications in long COVID detected by two electronic databases</strong> - Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a wide range of acute and chronic complications including long COVID, a well-known chronic sequela. Long COVID often necessitates long-term treatment, which may lead to an increased potential for drug-drug interactions (DDIs). The objective of this study was to assess potential DDIs among frequently prescribed medications in long COVID by using two electronic databases. Sixty frequently prescribed agents were…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Engineered Nanovesicles Expressing Bispecific Single Chain Variable Fragments to Protect against SARS-CoV-2 Infection</strong> - Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in high morbidity and mortality rates worldwide. Although the epidemic has been controlled in many areas and numerous patients have been successfully treated, the risk of reinfection persists due to the low neutralizing antibody titers and weak immune response. To provide long-term immune protection for infected patients, novel bispecific CB6/dendritic cell (DC)-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>Molecular Design of Novel Inhibitor by TargetingIL-6Rα using Combined Pharmacophore and Experimentally Verified Plant Products with Scaffold-Hopping Techniques: A Dual Therapeutic Strategy for COVID-19 and Cancer</strong> - The IL-6/IL-6R/gp130 complex serves as a significant indicator of cytokine release syndrome in COVID-19 and chronic inflammation, increasing the risk of cancer. Therefore, we identified IL-6Rα as a potential target to block gp130 interaction. Notably, there has been no reception of approval for an orally available drug to serve this purpose, to date. In this study, we targeted IL-6Rα to inhibit IL-6Rα/gp130 interaction. The selection of the lead candidate L821 involved the amalgamation of three…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity</strong> - Hepatitis C virus (HCV) exploits the four entry factors CD81, scavenger receptor class B type I (SR-BI, also known as SCARB1), occludin, and claudin-1 as well as the co-factor epidermal growth factor receptor (EGFR) to infect human hepatocytes. Here, we report that the disintegrin and matrix metalloproteinase 10 (ADAM10) associates with CD81, SR-BI, and EGFR and acts as HCV host factor. Pharmacological inhibition, siRNA-mediated silencing and genetic ablation of ADAM10 reduced HCV infection….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-based virtual screening, ADMET analysis, and molecular dynamics simulation of Moroccan natural compounds as candidates for the SARS-CoV-2 inhibitors</strong> - The lack of treatments and vaccines effective against SARS-CoV-2 has forced us to explore natural compounds that could potentially inhibit this virus. Additionally, Morocco is renowned for its rich plant diversity and traditional medicinal uses, which inspires us to leverage our cultural heritage and the abundance of natural resources in our country for therapeutic purposes. In this study, an extensive investigation was conducted to gather a collection of phytoconstituents extracted from…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The double-edged sword of the hippocampus-ventromedial prefrontal cortex resting-state connectivity in stress susceptibility and resilience: A prospective study</strong> - The hippocampus has long been considered a pivotal region implicated in both stress susceptibility and resilience. A wealth of evidence from animal and human studies underscores the significance of hippocampal functional connectivity with the ventromedial prefrontal cortex (vmPFC) in these stress-related processes. However, there remains a scarcity of research that explores and contrasts the roles of hippocampus-vmPFC connectivity in stress susceptibility and resilience when facing a real-life…</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>Influenza A virus replication has a stronger dependency on Raf/MEK/ERK signaling pathway activity than SARS-CoV-2</strong> - The recent COVID-19 pandemic again highlighted the urgent need for broad-spectrum antivirals, both for therapeutic use in acute viral infection and for pandemic preparedness in general. The targeting of host cell factors hijacked by viruses during their replication cycle presents one possible strategy for development of broad-spectrum antivirals. By inhibiting the Raf/MEK/ERK signaling pathway, a central kinase cascade of eukaryotic cells, which is being exploited by numerous viruses of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Coffee as a dietary strategy to prevent SARS-CoV-2 infection</strong> - CONCLUSIONS: This study verified moderate coffee consumption, including decaffeination, can provide a new guideline for the prevention of SARS-CoV-2. Based on the results, we also suggest a coffee-drinking plan for people to prevent infection in the post-COVID-19 era.</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>Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8+ T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine</strong> - CONCLUSION: TIGIT expression on CD8+ T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8+ T cells, thereby enhancing the effectiveness of vaccination.</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>Intranasal G5-BGG/pDNA vaccine elicits protective systemic and mucosal immunity against SARS-CoV-2 by transfecting mucosal dendritic cells</strong> - Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines that provide both disease protection and transmission inhibition. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal-associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5-BGG and antigen-expressing plasmid DNA…</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>Colloidal aggregation confounds cell-based Covid-19 antiviral screens</strong> - Colloidal aggregation is one of the largest contributors to false-positives in early drug discovery and chemical biology. Much work has focused on its impact on pure-protein screens; here we consider aggregations role in cell-based infectivity assays in Covid-19 drug repurposing. We began by investigating the potential aggregation of 41 drug candidates reported as SARs-CoV-2 entry inhibitors. Of these, 17 formed colloidal-particles by dynamic light scattering and exhibited detergent-dependent…</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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