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<title>12 July, 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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<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>A novel method to accurately estimate pathway activity in single cells for clustering and differential analysis</strong> -
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Inferring which and how biological pathways and gene sets are changing is a key question in many studies that utilize single-cell RNA sequencing. Typically, these questions are addressed by quantifying the enrichment of known gene sets in lists of genes derived from global analysis. Here we offer a new method to first infer pathway activity in each cell. This allows more sensitive differential analysis and utilizing pathway scores to cluster cells and compute UMAP or other similar projections. We apply our method on datasets of COVID-19 and glioblastoma, and demonstrate its utility. SiPSiC analysis is consistent with findings reported by previous analyses in many cases, but also reveals the differential expression of novel pathways, enabling us to suggest new mechanisms underlying the pathophysiology of these diseases and demonstrating SiPSiC’s high accuracy and sensitivity in detecting biological function and traits. In addition, we demonstrate how it can be used to better classify cells based on activity of biological pathways instead of single genes and its ability to overcome patient specific artifacts.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.03.27.534310v2" target="_blank">A novel method to accurately estimate pathway activity in single cells for clustering and differential analysis</a>
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</div></li>
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<li><strong>Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor binding domain (RBD)</strong> -
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Second-generation COVID-19 vaccines with improved immunogenicity (e.g., breadth, duration) and availability (e.g., lower costs, refrigerator stable) are needed to enhance global coverage. In this work, we formulated a clinical-stage SARS-CoV-2 receptor binding domain (RBD) virus-like particle (VLP) vaccine candidate (IVX-411) with widely available adjuvants. Specifically, we assessed the in vitro storage stability and in vivo mouse immunogenicity of IVX-411 formulated with aluminum-salt adjuvants (Alhydrogel, AH and Adjuphos, AP), without or with the TLR-9 agonist CpG-1018 (CpG), and compared these profiles to IVX-411 adjuvanted with an oil-in-water nano-emulsion (AddaVax, AV). Although IVX-411 bound both AH and AP, lower binding strength of antigen to AP was observed by Langmuir binding isotherms. Interestingly, AH- and AP-adsorbed IVX-411 had similar storage stability profiles as measured by antigen binding assays (competitive ELISAs), but the latter displayed higher pseudovirus neutralizing titers (pNT) in mice, at levels comparable to titers elicited by AV-adjuvanted IVX-411. CpG addition to alum (AP or AH) resulted in a marginal trend of improved pNTs in stressed samples only, yet did not impact the storage stability profiles of IVX-411. In contrast, previous work with AH-formulations of a monomeric RBD antigen showed greatly improved immunogenicity and decreased stability upon CpG addition to alum. At elevated temperatures (25, 37{degrees}C), IVX-411 formulated with AH or AP displayed decreased in vitro stability compared to AV-formulated IVX-411and this rank-ordering correlated with in vivo performance (mouse pNT values). This case study highlights the importance of optimizing antigen-adjuvant interactions to develop low cost, aluminum-salt adjuvanted recombinant subunit vaccine candidates.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.10.548406v1" target="_blank">Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor binding domain (RBD)</a>
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<li><strong>An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV</strong> -
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The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.10.548424v1" target="_blank">An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV</a>
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<li><strong>Studies on the selectivity of the SARS-CoV-2 papain-like protease reveal the importance of the P2’ proline of the viral polyprotein</strong> -
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<div>
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The SARS-CoV-2 papain-like protease (PLpro) is an antiviral drug target that catalyzes the hydrolysis of the viral polyproteins pp1a/1ab, releasing the non-structural proteins (nsps) 1-3 that are essential for the coronavirus lifecycle. The LXGG{downarrow}X motif found in pp1a/1ab is crucial for recognition and cleavage by PLpro. We describe molecular dynamics, docking, and quantum mechanics/molecular mechanics (QM/MM) calculations to investigate how oligopeptide substrates derived from the viral polyprotein bind to PLpro. The results reveal how the substrate sequence affects the efficiency of PLpro-catalyzed hydrolysis. In particular, a proline at the P2'; position promotes catalysis, as validated by residue substitutions and mass spectrometry-based analyses. Analysis of PLpro catalyzed hydrolysis of LXGG motif-containing oligopeptides derived from human proteins suggests that factors beyond the LXGG motif and the presence of a proline residue at P2' contribute to catalytic efficiency, possibly reflecting the promiscuity of PLpro. The results will help in identifying PLpro substrates and guiding inhibitor design.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.11.548309v1" target="_blank">Studies on the selectivity of the SARS-CoV-2 papain-like protease reveal the importance of the P2’ proline of the viral polyprotein</a>
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<li><strong>Impact of non-pharmaceutical interventions on COVID-19 incidence and deaths: cross-national natural experiment in 32 European countries</strong> -
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Purpose: Non-pharmaceutical interventions (NPIs) have been the cornerstone of COVID-19 pandemic control, but evidence on their effectiveness varies according to the methods and approaches taken to empirical analysis. We analysed the impact of NPIs on incident SARS-CoV-2 across 32 European countries (March-December 2020) using two NPI trackers: the Corona Virus Pandemic Policy Monitor (COV-PPM), and the Oxford Covid-19 Government Response Tracker (OxCGRT). Methods: NPIs were summarized through principal component analysis into three sets, stratified by two waves (C1-C3, weeks 5-25, and C4-C6, weeks 35-52). Longitudinal, multi-level mixed-effects negative binomial regression models were fitted to estimate incidence rate ratios for cases and deaths considering different time-lags and reverse causation (i.e. changing incidence causing NPIs), stratified by waves and geographical regions (Western, Eastern, Northern, Southern, Others). Results: During the first wave, restrictions on movement/mobility, public transport, public events, and public spaces (C1) and healthcare system improvements, border closures and restrictions to public institutions (C2) reduced SARS-CoV-2 incidence after 28 and 35-days. Mask policies (C3) reduced SARS-CoV-2 incidence (except after 35-days). During wave 1, C1 and C2 reduced deaths after 49-days and C3 after 21, 28 and 35-days. During wave 2, restrictions on movement/mobility, public transport and healthcare system improvements (C5) decreased SARS-CoV-2 cases and deaths across all countries. Conclusion: In the absence of pre-existing immunity, vaccines or treatment options, the impact of NPIs on SARS-CoV-2 incidence and deaths varied by regions and waves but was consistent across components of NPIs derived from two policy trackers (CoV-PPM and OxCGRT).
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.07.11.22277491v2" target="_blank">Impact of non-pharmaceutical interventions on COVID-19 incidence and deaths: cross-national natural experiment in 32 European countries</a>
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<li><strong>Warmth and competence perceptions of key protagonists are associated with containment measures during the COVID-19 pandemic: Evidence from 35 countries</strong> -
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It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (Ntotal = 12,553) from six continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions – warmth and competence – plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/8xgb5/" target="_blank">Warmth and competence perceptions of key protagonists are associated with containment measures during the COVID-19 pandemic: Evidence from 35 countries</a>
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<li><strong>A Novel Artificial Intelligence and Machine learning-based scoring system for evaluating re-purposing potential of Valproic Acid drug in COVID-19.</strong> -
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Background Despite widespread vaccinations and the introduction of many repurposed medications, the rise of COVID-19 reinfection due to the SARS-CoV Omicron (B.1.1.529) variant has presented a significant challenge to health authorities across the world. There is a critical need for novel healthcare medications. Valproic acid (VPA) has been reported to be a beneficial drug due to its excellent property to hinder enveloped viral multiplication. Artificial Intelligence (AI) and Machine Learning (ML) have been used extensively to predict the repurposing potential of a drug by examining its past couple of years’ activity. The strategies for drug repositioning that will play a substantial role in this approach can be widely categorized into AI approaches, network-based models, and structure-based approaches. Methodology We have implemented a multimodal pipeline that operates on computational and machine learning strategies, namely molecular docking, molecular data, chemical information, clinical data, and gene expression to analyze the drugs for their sensitivity against covid-19. Here, we implemented the COV-DrugX pipeline to comprehend the physicochemical properties of VPA interactions with viral protein (targets), identify a place in the gene expression profile, additionally its potential role in human network databases. Result and Conclusion Here, we have analyzed the ML pipeline developed by our research group (Rawal et al., 2021) to identify the COVID-associated drug repurposing properties through AI and learning prediction module and use the COV-DrugX pipeline, that predicts the repurposing properties between different existing COVID-19 drugs. Nsp13 was found to have the highest binding affinity (-5.6 kcal/mol) with VPA. By using different modules, we have found that VPA displays physicochemical, biological, and other characteristics similar to existent COVID-19 drugs.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/adb82/" target="_blank">A Novel Artificial Intelligence and Machine learning-based scoring system for evaluating re-purposing potential of Valproic Acid drug in COVID-19.</a>
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<li><strong>OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide, and methotrexate monitoring, and factors associated with change in monitoring rate.</strong> -
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Background: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study aimed to investigate if disease-modifying anti-rheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. Methods: A population-based cohort study was conducted with the approval of NHS England, using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP9s SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide, or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. Findings: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (Leflunomide: +20.7 percentage points), and monitoring tests (Blood Pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Substantial and consistent differences were observed in overall missed monitoring rates between several groups throughout the study. Interpretation: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions, and patient groups, highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should aim to evaluate the causes of the differences identified between groups. Funding: None. Keywords COVID-19, electronic health records, general practice, primary health care, antirheumatic agents, methotrexate, azathioprine, leflunomide.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.06.23290826v3" target="_blank">OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide, and methotrexate monitoring, and factors associated with change in monitoring rate.</a>
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<li><strong>Characteristics and quality of studies pertaining to masks published in the Morbidity and Mortality Weekly Report</strong> -
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Importance: Because the MMWR has substantial influence on United States public health policy and is not externally peer-reviewed, it is critical to understand the scientific process within the journal. Mask policies during COVID is one topic that has been highly influenced by data published in the MMWR. Objective: To describe and evaluate the nature and methodology of the reports and appropriateness of conclusions in MMWR pertaining to masks. Design, Setting and Participants: Retrospective cross-sectional study of MMWR publications pertaining to masks from 1978 to 2023. Main outcome measures: Study date, design, disease focus, setting, population and location. Whether the study was able to assess mask effectiveness, if results were statistically significant, if masks were concluded to be effective, if randomized evidence and/or conflicting data was mentioned or cited, if causal statements were made about effectiveness, and, if so, whether they were appropriate. Results: 77 studies, all published after 2019, met our inclusion criteria. 75/77 (97.4%) studies were from the United States alone. All geographic regions and age groups were represented. The most common study design was observational without a comparator group 22/77 (28.6%). The most common setting was the community (35/77;45.5%). 0/77 were randomized studies. 23/77 (29.9%) assessed mask effectiveness, with 11/77 (14.3%) being statistically significant, but 58/77 (75.3%) stated masks were effective. Of these, 41/58 (70.7%) used causal language. Only one mannequin study used causal language appropriately (1.3%). 72/77 (93.5%) pertained to SARS-CoV-2 alone. None cited randomized data. 1/77 (1.3%) cited conflicting evidence. Conclusions and Relevance: MMWR publications pertaining to masks drew positive conclusions about mask effectiveness over 75% of the time despite only 30% testing masks and <15% having statistically significant results. No studies were randomized, yet over half drew causal conclusions. The level of evidence generated was low and the conclusions drawn were most often unsupported by the data. Our findings raise concern about the reliability of the journal for informing health policy.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.07.23292338v1" target="_blank">Characteristics and quality of studies pertaining to masks published in the Morbidity and Mortality Weekly Report</a>
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<li><strong>COVID-19, Family Dynamics, and Perceived Mental Health Among Families in Singapore</strong> -
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The COVID-19 pandemic presents a significant challenge to the lives and well-being of families with underaged children. Although previous studies have documented COVID-related deterioration in well-being and identified protective and risk factors, the mechanisms under which the pandemic leads to worsened well-being remain unclear. In addition, from a policymaker’s perspective, it is important to differentiate between the effects of government-issued infection control measures (such as lockdown) and families’ voluntary responses when facing the coronavirus (such as self-quarantine) on well-being. Using Singapore as an example, we collected retrospective self-reports on the everyday activities, stressors, and well-being of parents and other caregivers at three timepoints: before local transmission (Pre-pandemic), after local transmission but before the “circuit breaker” (Pandemic), and during the “circuit breaker” (Lockdown). We estimated the effects of the pandemic itself and families’ voluntary responses to it by contrasting Pandemic against Pre-pandemic, and we estimated the additional effects of imposed lockdown measures by contrasting Lockdown against Pandemic. Results showed significant changes in jobs and income, childcare arrangement, family dynamics, and parents’ emotional well-being throughout the three timepoints. Both mothers and fathers reported to worry most about the health and safety of family members and self. Mothers’ time spent on housework partially mediated the effect of lockdown on their emotional well-being, and parents’ conflict with other adults in the household partially mediated the effects of both pandemic and lockdown on their emotional well-being. The effects of pandemic and lockdown were also moderated by parents’ age, education level, and fathers’ authoritarian values.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/b3cua/" target="_blank">COVID-19, Family Dynamics, and Perceived Mental Health Among Families in Singapore</a>
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</div></li>
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<li><strong>How the COVID-19 pandemic impacted the perception of climate change in the UK</strong> -
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Forthcoming in American Behavioral Scientist (ABS) The COVID-19 pandemic erupted during the climate change (CC) crisis, forcing individuals to adapt abruptly to a new scenario, and triggering changes in everyone’s lifestyles. Based on a representative sample of the UK population (N= 1013) this paper investigates how the COVID-19 pandemic invited/forced individuals to reflect upon a new sustainable way of life and to (re)consider the anthropogenic impact on the environment. The results show that age and education are negatively associated with skepticism relating to the human impact on CC, while other control variables such as income, gender and employment status, have a limited impact on this attitude toward CC. Secondly, findings indicate a clear separation between those with a minimal standard of education, who support the natural origin of CC, while individuals with a higher level of education believe that CC is caused by human actions. Finally, on average, younger and more educated individuals tend to associate the COVID-19 pandemic with an opportunity to promote an eco-friendly world and to adopt an eco-sustainable approach.
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🖺 Full Text HTML: <a href="https://osf.io/46szu/" target="_blank">How the COVID-19 pandemic impacted the perception of climate change in the UK</a>
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<li><strong>Genomic Surveillance of SARS-CoV-2 Using Long-Range PCR Primers</strong> -
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Whole Genome Sequencing (WGS) of the SARS-CoV-2 virus is crucial in the surveillance of the COVID-19 pandemic. Several primer schemes have been developed to sequence the ~30,000 nucleotide SARS-CoV-2 genome that use a multiplex PCR approach to amplify cDNA copies of the viral genomic RNA. Midnight primers and ARTIC V4.1 primers are the most popular primer schemes that can amplify segments of SARS-CoV-2 (400 bp and 1200 bp, respectively) tiled across the viral RNA genome. Mutations within primer binding sites and primer-primer interactions can result in amplicon dropouts and coverage bias, yielding low-quality genomes with 'Ns' inserted in the missing amplicon regions, causing inaccurate lineage assignments, and making it challenging to monitor lineage-specific mutations in Variants of Concern (VoCs). This study uses seven long-range PCR primers with an amplicon size of ~4500 bp to tile across the complete SARS-CoV-2 genome. One of these regions includes the full-length S-gene by using a set of flanking primers. Using a small set of long-range primers to sequence SARS-CoV-2 genomes reduces the possibility of amplicon dropout and coverage bias.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.10.548464v1" target="_blank">Genomic Surveillance of SARS-CoV-2 Using Long-Range PCR Primers</a>
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<li><strong>Mora: abundance aware metagenomic read re-assignment for disentangling similar strains</strong> -
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Taxonomic classification of reads obtained by metagenomic sequencing is often a first step for understanding a microbial community, but correctly assigning sequencing reads to the strain or sub-species level has remained a challenging computational problem. We introduce Mora, a MetagenOmic read Re-Assignment algorithm capable of assigning short and long metagenomic reads with high precision, even at the strain level. Mora is able to accurately re-assign reads by first estimating abundances through an expectation-maximization algorithm and then utilizing abundance information to re-assign query reads. The key idea behind Mora is to maximize read re-assignment qualities while simultaneously minimizing the difference from estimated abundance levels, allowing Mora to avoid over assigning reads to the same genomes. On simulated diverse reads, this allows Mora to achieve F1 scores comparable to other algorithms while having less runtime. However, Mora significantly outshines other algorithms on very similar reads. We show that the high penalty of over assigning reads to a common reference genome allows Mora to accurately infer correct strains for real data in the form of short E. coli reads and long Covid-19 reads.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.10.18.512733v3" target="_blank">Mora: abundance aware metagenomic read re-assignment for disentangling similar strains</a>
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<li><strong>High-resolution map of the Fc-functions mediated by COVID-19 neutralizing antibodies</strong> -
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A growing body of evidence shows that Fc-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc-functions. Surprisingly, we found that nAbs with the most potent Fc-function recognize the N-terminal domain, followed by those targeting Class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the Class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc-functions. The divergent properties of the neutralizing and Fc-function mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc-functions of polyclonal sera differ from the profile observed with nAbs, suggesting that not-neutralizing antibodies also contribute to Fc-functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies and the evaluation of correlates of protection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.10.548360v1" target="_blank">High-resolution map of the Fc-functions mediated by COVID-19 neutralizing antibodies</a>
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<li><strong>Proteome profiling of nasopharynx reveals pathophysiological signature of COVID-19 disease severity</strong> -
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An aberrant innate immune system caused by the beta coronavirus SARS-CoV-2 is a characteristic manifestation of severe coronavirus disease 2019 (COVID-19). Here, we performed proteome profiling of nasopharyngeal (NP) swabs from 273 hospitalized patients with mild and severe COVID-19 symptoms, including non-survivors. We identified depletion in STAT1-mediated type I interferon response, retinol metabolism and NRF2 antioxidant system that are associated with disease severity in our patient demography. We found that the dysregulation of glucocorticoid signaling and renin-angiotensin-aldosterone system (RAAS) contribute to the pathophysiology of COVID-19 fatality. Hyperactivation of host innate immune system was observed in severe patients, marked by elevated proteins involved in neutrophil degranulation and platelet aggregation. Our study using high-throughput proteomics on the nasopharynx of COVID-19 patients provides additional evidence on the SARS-CoV-2-induced pathophysiological signatures of disease severity and fatality.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.09.548285v1" target="_blank">Proteome profiling of nasopharynx reveals pathophysiological signature of COVID-19 disease severity</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>Homologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 Subunit Recombinant Protein Vaccine<br/><b>Sponsor</b>: PT Bio Farma<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>Role of Ivermectin and Colchicine in Treatment of COVID-19: Randomized Controlled Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Ivermectin Tablets; Drug: Colchicine 0.5 MG; Drug: Standared managment<br/><b>Sponsor</b>: Ain Shams University<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of A Recombinant Protein COVID-19 Vaccine as Booster Vaccines</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E-2; Biological: SCTV01E<br/><b>Sponsor</b>: Sinocelltech Ltd.<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>COVID-19 Vaccine Hesitancy Counseling Intervention for Pharmacists</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Behavioral: Standard implementation webinar and online training; Behavioral: Virtual facilitation<br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; University of Arkansas; University of South Carolina; National Institute on Minority Health and Health Disparities (NIMHD)<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>LUSZ Treatment Efficacy in Hospitalized COVID-19 Patients</strong> - <b>Conditions</b>: COVID-19; Hospitalized COVID-19 Patients<br/><b>Interventions</b>: Drug: Lopinavir / Ritonavir; Drug: Remdesivir (RDV); Drug: Tocilizumab; Other: Corticosteroid Therapy-enhanced Standard Care (CTSC)<br/><b>Sponsors</b>: Lebanese University; Hospital Saydet Zgharta University Medical Center<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Developing an Effective Intervention to Address Post-Corona-Virus-Disease-2019 Balance Disorders, Weakness and Muscle Fatigue in Individuals Aged 65+</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: Resistance Training<br/><b>Sponsor</b>: Józef Piłsudski University of Physical Education<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>Multimodal Long Covid19</strong> - <b>Condition</b>: Long COVID-19 Syndrome<br/><b>Intervention</b>: Other: Multimodal intervention in Long Covid19<br/><b>Sponsors</b>: Universidad de Magallanes; Teaching Assistance and Research Center of the University of Magallanes CADI-UMAG; Clinical Hospital Dr. Lautaro Navarro Avaria<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1/2 Safety and Immunogenicity Trial of COVID-19 Vaccine COVIVAC (Phase 2)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVIVAC vaccine<br/><b>Sponsors</b>: Institute of Vaccines and Medical Biologicals, Vietnam; National Institute of Hygiene and Epidemiology (NIHE), Vietnam; Center for Disease Control of Thai Binh Province, Vietnam<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>Efficiency and Safety of Paxlovid for COVID-19 Patients With Severe Chronic Kidney Disease</strong> - <b>Conditions</b>: COVID-19; Renal Insufficiency, Chronic<br/><b>Intervention</b>: Drug: Nirmatrelvir/ritonavir<br/><b>Sponsor</b>: Chinese PLA General Hospital<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of SCB-2023 Vaccine as a Booster in Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: SCB-2023 vaccine (trivalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection; Biological: SCB-2019 (monovalent), a recombinant SARS-CoV-2 trimeric S-protein subunit vaccine for COVID-19; intramuscular injection<br/><b>Sponsor</b>: Clover Biopharmaceuticals AUS Pty Ltd<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 Immunogenicity Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB002</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: LYB002V14; Biological: LYB002V14A; Biological: LYB002CA<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2/3 Heterologous Boosting Study With Different Dose Levels of Monovalent SARS-CoV-2 rS Vaccines</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: NVX-CoV2373 (5μg); Biological: NVX-CoV2601 (5μg); Biological: NVX-CoV2601(5μg); Biological: NVX-CoV2601 (35μg); Biological: NVX-CoV2601(35μg); Biological: NVX-CoV2601(50μg); Biological: Bivalent BA.4/5<br/><b>Sponsor</b>: Novavax<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 Immunogenicity and Safety Following a Heterologous Booster Dose of Recombinant SARS-CoV-2 Vaccine LYB001</strong> - <b>Conditions</b>: COVID-19; Vaccine Reaction<br/><b>Interventions</b>: Biological: LYB001; Biological: CoronaVac<br/><b>Sponsors</b>: Guangzhou Patronus Biotech Co., Ltd.; Yantai Patronus Biotech Co., Ltd.; Affiliated Hospital of North Sichuan Medical College<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>: Asthenia; COVID-19; Functional MRI; Cognitive Impairment<br/><b>Interventions</b>: Other: Structural and functional MRI; Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<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>Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome</strong> - <b>Condition</b>: Post-Acute COVID-19 Syndrome<br/><b>Interventions</b>: Drug: Placebo; Drug: Anakinra 149 MG/ML Prefilled Syringe [Kineret]<br/><b>Sponsor</b>: Hellenic Institute for the Study of Sepsis<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>Structure-based discovery of thiosemicarbazones as SARS-CoV-2 main protease inhibitors</strong> - Aim: Discovery of novel SARS-CoV-2 main protease (M^(pro)) inhibitors using a structure-based drug discovery strategy. Materials & methods: Virtual screening employing covalent and noncovalent docking was performed to discover M^(pro) inhibitors, which were subsequently evaluated in biochemical and cellular assays. Results: 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 M^(pro) with IC(50) values of 0.4-3 μM. They were also…</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 sulphonamide-tethered <em>N</em>-((triazol-4-yl)methyl)isatin derivatives as inhibitors of SARS-CoV-2 main protease</strong> - SARS-CoV-2 pandemic in the end of 2019 led to profound consequences on global health and economy. Till producing successful vaccination strategies, the healthcare sectors suffered from the lack of effective therapeutic agents that could control the spread of infection. Thus, academia and the pharmaceutical sector prioritise SARS-CoV-2 antiviral drug discovery. Here, we exploited previous reports highlighting the anti-SARS-CoV-2 activities of isatin-based molecules to develop novel…</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 phosphodiesterase 12 results in antiviral activity against several RNA viruses including SARS-CoV-2</strong> - The 2’,5’- oligoadenylate synthetase (OAS) - ribonuclease L (RNAseL) - phosphodiesterase 12 (PDE12) pathway is an essential interferon-induced effector mechanism against RNA virus infection. Inhibition of PDE12 leads to selective amplification of RNAseL activity in infected cells. We aimed to investigate PDE12 as a potential pan-RNA virus antiviral drug target and develop PDE12 inhibitors that elicit antiviral activity against a range of viruses. A library of 18 000 small molecules was screened…</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>Mitochondria of lung venular capillaries mediate lung-liver crosstalk in pneumonia</strong> - Failure of the lung’s endothelial barrier underlies lung injury, which causes the high mortality Acute Respiratory Distress Syndrome (ARDS). Multiple organ failure predisposes to the mortality, but mechanisms are poorly understood. Here, we show that mitochondrial Uncoupling Protein 2 (UCP2), a component of the mitochondrial inner membrane, plays a role in the barrier failure. Subsequent lung-liver crosstalk mediated by neutrophil activation causes liver congestion. We intranasally instilled…</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>Cereals as a Source of Bioactive Compounds with Anti-Hypertensive Activity and Their Intake in Times of COVID-19</strong> - Cereals have phytochemical compounds that can diminish the incidence of chronic diseases such as hypertension. The angiotensin-converting enzyme 2 (ACE2) participates in the modulation of blood pressure and is the principal receptor of the virus SARS-CoV-2. The inhibitors of the angiotensin-converting enzyme (ACE) and the block receptors of angiotensin II regulate the expression of ACE2; thus, they could be useful in the treatment of patients infected with SARS-CoV-2. The inferior peptides 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>Recent advances in cholinergic mechanisms as reactions to toxicity, stress, and neuroimmune insults</strong> - This review presents recent studies of the chemical and molecular regulators of acetylcholine (ACh) signaling and the complexity of the small molecule and RNA regulators of those mechanisms that control cholinergic functioning in health and disease. The underlying structural, neurochemical, and transcriptomic concepts, including basic and translational research and clinical studies, shed new light on how these processes inter-change under acute states, age, sex, and COVID-19 infection; all 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>Identification of alpha-linolenic acid as a broad-spectrum antiviral against zika, dengue, herpes simplex, influenza virus and SARS-CoV-2 infection</strong> - Zika virus (ZIKV) has garnered global attention due to its association with severe congenital defects including microcephaly. However, there are no licensed vaccines or drugs against ZIKV infection. Pregnant women have the greatest need for treatment, making drug safety crucial. Alpha-linolenic acid (ALA), a polyunsaturated ω-3 fatty acid, has been used as a health-care product and dietary supplement due to its potential medicinal properties. Here, we demonstrated that ALA inhibits ZIKV…</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>Mechanism of the Covalent Inhibition of Human Transmembrane Protease Serine 2 as an Original Antiviral Strategy</strong> - The Transmembrane Protease Serine 2 (TMPRSS2) is a human enzyme which is involved in the maturation and post-translation of different proteins. In addition to being overexpressed in cancer cells, TMPRSS2 plays a further fundamental role in favoring viral infections by allowing the fusion of the virus envelope with the cellular membrane, notably in SARS-CoV-2. In this contribution, we resort to multiscale molecular modeling to unravel the structural and dynamical features of TMPRSS2 and its…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Smoke and Spike: Benzo[a]pyrene Enhances SARS-CoV-2 Infection by Boosting NR4A2-Induced ACE2 and TMPRSS2 Expression</strong> - Cigarette smoke aggravates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the underlying mechanisms remain unclear. Here, they show that benzo[a]pyrene in cigarette smoke extract facilitates SARS-CoV-2 infection via upregulating angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). Benzo[a]pyrene trans-activates the promoters of ACE2 and TMPRSS2 by upregulating nuclear receptor subfamily 4 A number 2 (NR4A2) and promoting its…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro</strong> - Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence. Methods: 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>Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2</strong> - Since the outbreak of the novel coronavirus nearly 3 years ago, the world’s public health has been under constant threat. At the same time, people’s travel and social interaction have also been greatly affected. The study focused on the potential host targets of SARS-CoV-2, CD13, and PIKfyve, which may be involved in viral infection and the viral/cell membrane fusion stage of SARS-CoV-2 in humans. In this study, electronic virtual high-throughput screening for CD13 and PIKfyve was conducted…</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>Investigation of oxidative, inflammatory and apoptotic effects of favipiravir use alone and combined with vitamin C on brain tissue of elderly rats</strong> - Favipiravir is a nucleoside analogue antiviral drug and inhibits the replication of many RNA viruses, especially influenza viruses. Favipiravir has also been used to treat patients with mild to moderate COVID-19 disease. However, various side effects, including neurological side effects, have been reported related to the use of favipiravir. Therefore, in this study, we aimed to investigate the possible effects of favipiravir alone or in combination with vitamin C on aged rats’ brain tissue and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>In silico</em> identification of D449-0032 compound as a putative SARS-CoV-2 M<sup>pro</sup> inhibitor</strong> - The SARS-CoV-2 pandemic originated the urgency in developing therapeutic resources for the treatment of COVID-19. Despite the current availability of vaccines and some antivirals, the occurence of severe cases of the disease and the risk of the emergence of new virus variants still motivate research in this field. In this context, this study aimed at the computational prospection of likely inhibitors of the main protease (M^(pro)) of SARS-CoV-2 since inhibiting this enzyme leads to disruption 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>Synthesis of multivalent sialyllactose-conjugated PAMAM dendrimers: Binding to SARS-CoV-2 spike protein and influenza hemagglutinin</strong> - Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) and influenza viruses have spread around the world at an unprecedented rate. Despite multiple vaccines, new variants of SARS-CoV-2 and influenza have caused a remarkable level of pathogenesis. The development of effective antiviral drugs to treat SARS-CoV-2 and influenza remains a high priority. Inhibiting viral cell surface attachment represents an early and efficient means to block virus infection. Sialyl glycoconjugates, on…</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>Nanobodies with cross-neutralizing activity provide prominent therapeutic efficacy in mild and severe COVID-19 rodent models</strong> - The weakened protective efficacy of COVID-19 vaccines and antibodies caused by SARS-CoV-2 variants presents a global health emergency, which underscores the urgent need for universal therapeutic antibody intervention for clinical patients. Here, we screened three alpacas-derived nanobodies (Nbs) with neutralizing activity from twenty RBD-specific Nbs. The three Nbs were fused with the Fc domain of human IgG, namely aVHH-11-Fc, aVHH-13-Fc and aVHH-14-Fc, which could specifically bind RBD protein…</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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