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167 lines
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<title>21 March, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<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>Validation of RT-qPCR primers and probes for new and old variants of SARS-CoV-2 in a world scale</strong> -
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<div>
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Introduction: The demand for molecular diagnosis of pathogens has surged dramatically since the onset of the COVID-19 pandemic. In this context, different diagnostic tests have been developed to identify SARS-CoV-2 in patient samples. The emergence of new variants of SARS-CoV-2 raises questions about whether the molecular tests available for diagnosis continue to be effective in detecting the virus in biological samples. Objective: This study analyzed the viability of molecular targets directed to N, E and RdRp genes available against the new variants of SARS-CoV-2. Methodology: For this, we used bioinformatics tools to analyze SARS-CoV-2 genomic data of different variants deposited in GSAID and NCBI virus genomic databases to assess the accuracy of molecular tests available for the diagnosis of COVID-19. We also developed software for analyzing mutation frequencies in different molecular targets from the mutation database. Results: Mutation frequency analysis revealed a high rate of mutations in the N, E and RdRp genes and targets, although the target regions were more conserved. Only three SNPs were recurrent in the sequences of the variants identified in different continents and all in different targets. On the other hand, the registered mutations are not consistent and do not appear frequently in isolates of the same variant in all regions of the world. Conclusion: Our data suggest that the molecular targets designed for the first SARS-CoV-2 variants remain valid for the identification of new virus variants despite the large number of identified haplotypes. However, false negative test failures can be identified by using more than one molecular target for the same sample. Genomic regions that are under evolutive selective pressure should be avoided in the use of the diagnostic, once the emergence of new variants may affect the efficiency of molecular testing on a global scale.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.19.585194v1" target="_blank">Validation of RT-qPCR primers and probes for new and old variants of SARS-CoV-2 in a world scale</a>
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</div></li>
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<li><strong>Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots</strong> -
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<div>
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Background: In the earliest days of COVID-19 pandemic, the collection of dried blood spots (DBS) enabled public health laboratories to undertake population-scale seroprevalence studies to estimate rates of SARS-CoV-2 exposure. With SARS-CoV-2 seropositivity levels now estimated to exceed 94% in the United States, attention has turned to using DBS to assess functional (neutralizing) antibodies within cohorts of interest. Methods: Contrived DBS eluates from convalescent, fully vaccinated and pre-COVID-19 serum samples were evaluated in SARS-CoV-2 plaque reduction neutralization titer (PRNT) assays, a SARS-CoV-2 specific 8-plex microsphere immunoassay, a cell-based pseudovirus assay, and two different spike-ACE2 inhibition assays. Results: DBS eluates from convalescent individuals were compatible with RBD-ACE2 inhibition assays, an in-house Luminex-based RBD-ACE2 inhibition assay, and commercial real-time PCR-based neutralization assay (NAB-Sure) but not cell-based pseudovirus assays or PRNT. The insensitivity of cell-based pseudovirus assays was overcome with DBS eluates from vaccinated individuals with high SARS-CoV-2 antibody titers. Conclusion: SARS-CoV-2 neutralizing titers can be derived with confidence from DBS eluates, thereby opening the door to the use of these biospecimens for the analysis of vulnerable populations and normally hard to reach communities.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.18.585599v1" target="_blank">Quantitating SARS-CoV-2 Neutralizing Antibodies from Human Dried Blood Spots</a>
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<li><strong>No Utilitarians in a Pandemic? Shifts in Moral Reasoning during the COVID-19 Global Health Crisis</strong> -
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<div>
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The COVID-19 pandemic poses many real-world moral dilemmas, which can pit the needs and rights of the many against the needs and rights of the few. We investigated the influence of this contemporary global crisis on moral judgments in older adults, who are at greatest personal risk from the pandemic. We hypothesized that during this pandemic, individuals would give fewer utilitarian responses to hypothetical dilemmas, accompanied by higher levels of confidence and emotion elicitation. Our pre-registered analysis (https://osf.io/g2wtp) involved two waves of data collection, before (2014) and during (2020) the COVID-19 pandemic, regarding three categories of moral dilemmas (personal rights, agent-centered permissions, and special obligations). While utilitarian responses considered across all categories of dilemma did not differ, participants during the 2020 wave gave fewer utilitarian responses to dilemmas involving personal rights; that is, they were less willing to violate the personal rights of others to produce the best overall outcomes.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/yjn3u/" target="_blank">No Utilitarians in a Pandemic? Shifts in Moral Reasoning during the COVID-19 Global Health Crisis</a>
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</div></li>
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<li><strong>Accurately estimating pathway activity in single cells for clustering and differential analysis</strong> -
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<div>
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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 SiPSiC, a new method to 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, lung adenocarcinoma and glioma, and demonstrate its utility. SiPSiC analysis is consistent with findings reported by previous analyses in many cases, but also reveals the differential activity 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/10.1101/2023.03.27.534310v3" target="_blank">Accurately estimating pathway activity in single cells for clustering and differential analysis</a>
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</div></li>
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<li><strong>Concepts and methods for predicting viral evolution</strong> -
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<div>
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The seasonal human influenza virus undergoes rapid evolution, leading to significant changes in circulating viral strains from year to year. These changes are typically driven by adaptive mutations, particularly in the antigenic epitopes, the regions of the viral surface protein haemagglutinin targeted by human antibodies. Here we describe a consistent set of methods for data-driven predictive analysis of viral evolution. Our pipeline integrates four types of data: (1) sequence data of viral isolates collected on a worldwide scale, (2) epidemiological data on incidences, (3) antigenic characterization of circulating viruses, and (4) intrinsic viral phenotypes. From the combined analysis of these data, we obtain estimates of relative fitness for circulating strains and predictions of clade frequencies for periods of up to one year. Furthermore, we obtain comparative estimates of protection against future viral populations for candidate vaccine strains, providing a basis for pre-emptive vaccine strain selection. Continuously updated predictions obtained from the prediction pipeline for influenza and SARS-CoV-2 are available on the website https://previr.app.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.19.585703v1" target="_blank">Concepts and methods for predicting viral evolution</a>
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</div></li>
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<li><strong>Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</strong> -
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<div>
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Codon optimization describes the process used to increase protein production by use of alternative but synonymous codon changes. In SARS-CoV-2 mRNA vaccines codon optimizations can result in differential secondary conformations that inevitably affect a protein’s function with significant consequences to the cell. Importantly, when codon optimization increases the GC content of synthetic mRNAs, there can be an inevitable enrichment of G-quartets which potentially form G-quadruplex structures. The emerging G-quadruplexes are favorable binding sites of RNA binding proteins like helicases that inevitably affect epigenetic reprogramming of the cell by altering transcription, translation and replication. In this study, we performed a RNAfold analysis to investigate alterations in secondary structures of mRNAs in SARS-CoV-2 vaccines due to codon optimization. We show a significant increase in the GC content of mRNAs in vaccines as compared to native SARS-CoV-2 RNA sequences encoding the spike protein. As the GC enrichment leads to more G-quadruplex structure formations, these may contribute to potential pathological processes initiated by SARS-CoV-2 molecular vaccination.
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🖺 Full Text HTML: <a href="https://osf.io/bcsa6/" target="_blank">Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease</a>
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<li><strong>Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanoparticles Made of Inexpensive Metals - Replacing Colloidal Gold</strong> -
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<div>
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Nanoparticles (NPs) can be conjugated with diverse biomolecules and employed in biosensing to detect target analytes in biological samples. This proven concept was primarily used during the COVID-19 pandemic with gold NPs-based lateral flow assays (LFAs). Considering the gold price and its worldwide depletion, here we show that novel plasmonic nanoparticles (NPs) based on inexpensive metals, titanium nitride (TiN) and copper covered with a gold shell (Cu@Au), perform comparable or even better than gold nanoparticles. After conjugation, these novel nanoparticles provided high figures of merit for LFA testing, such as high signals and specificity and robust naked-eye signal recognition. To the best of our knowledge, our study represents the 1st application of laser-ablation-fabricated nanoparticles (TiN) in the LFA and dot-blot biotesting. Since the main cost of the Au NPs in commercial testing kits is in the colloidal synthesis, our development with TiN is very exciting, offering potentially very inexpensive plasmonic nanomaterials for various bio-testing applications. Moreover, our machine learning study showed that the bio-detection with TiN is more accurate than that with Au.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.08.574723v2" target="_blank">Lateral Flow Assays Biotesting by Utilizing Plasmonic Nanoparticles Made of Inexpensive Metals - Replacing Colloidal Gold</a>
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<li><strong>Hidden evolutionary constraints dictate the retention of coronavirus accessory genes</strong> -
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Coronaviruses exhibit many mechanisms of genetic innovation (1-5), including the acquisition of accessory genes that originate by capture of cellular genes or through duplication of existing viral genes (6,7). Accessory genes influence viral host range and cellular tropism, but little is known about how selection acts on these variable regions of virus genomes. We used experimental evolution of mouse hepatitis virus (MHV) encoding a cellular AKAP7 phosphodiesterase and an inactive native phosphodiesterase, NS2 (ref 8) to simulate the capture of a host gene and analyze its evolution. After courses of serial infection, the gene encoding inactive NS2, ORF2, unexpectedly remained intact, suggesting it is under cryptic constraint uncoupled from the function of NS2. In contrast, AKAP7 was retained under strong selection but rapidly lost under relaxed selection. Guided by the retention of ORF2 and similar patterns in related betacoronaviruses, we analyzed ORF8 of SARS-CoV-2, which arose via gene duplication6 and contains premature stop codons in several globally successful lineages. As with MHV ORF2, the coding-defective SARS-CoV-2 ORF8 gene remains largely intact, mirroring patterns observed during MHV experimental evolution, challenging assumptions on the dynamics of gene loss in virus genomes and extending these findings to viruses currently adapting to humans.
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</div>
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.12.561935v2" target="_blank">Hidden evolutionary constraints dictate the retention of coronavirus accessory genes</a>
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<li><strong>Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries</strong> -
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<div>
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In vitro screening of large libraries of compounds with automated High-throughput screening is expensive, time consuming and requires dedicated infrastructures. Conversely, the screening of DNA-encoded chemical libraries can be rapidly performed with basic equipment available in most laboratories. In this study we identified novel inhibitors of SARS-CoV-2 main protease (Mpro) through the affinity screening of the commercially available ''DELopen'' library, containing 4.2 billion compounds. The identified inhibitors were peptidomimetics compounds containing a C-terminal electrophilic group able to covalently bind to Mpro reactive Cys145 (confirmed by x-ray crystallography). Compound SLL11 had IC50 = 30nM and was found to be well optimized, proving that the rapid exploration of large chemical spaces, enabled by DECL technology, allows the direct identification of potent inhibitors avoiding several rounds of iterative medicinal chemistry. Compound MP6, a close analogue of SLL11, showed antiviral activity against SARS-CoV-2 in the low micromolar range when tested in Caco-2 and Calu-3 (EC50 = 2.3 M) cell lines. As peptidomimetics compounds can suffer from low cell permeability and metabolic stability, the cyclization of the compounds as well as the substitution of selected residues with D-enantiomers will be explored in the future to improve the antiviral activity of these novel compounds.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.16.585341v1" target="_blank">Identification of unique and potent inhibitors of SARS-CoV-2 main protease from DNA-encoded chemical libraries</a>
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<li><strong>A Protein Language Model for Exploring Viral Fitness Landscapes</strong> -
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<div>
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Successively emerging SARS-CoV-2 variants lead to repeated epidemic surges through escalated spreading potential (i.e., fitness). Modeling genotype-fitness relationship enables us to pinpoint the mutations boosting viral fitness and flag high-risk variants immediately after their detection. Here, we introduce CoVFit, a protein language model able to predict the fitness of variants based solely on their spike protein sequences. CoVFit was trained with genotype-fitness data derived from viral genome surveillance and functional mutation data related to immune evasion. When limited to only data available before the emergence of XBB, CoVFit successfully predicted the higher fitness of the XBB lineage. Fully-trained CoVFit identified 549 fitness elevation events throughout SARS-CoV-2 evolution until late 2023. Furthermore, a CoVFit-based simulation was able to predict the higher fitness of JN.1 subvariants before their detection. Our study provides both insight into the SARS-CoV-2 fitness landscape and a novel tool potentially transforming viral genome surveillance.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.15.584819v1" target="_blank">A Protein Language Model for Exploring Viral Fitness Landscapes</a>
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<li><strong>Modulation of SARS-CoV-2 spike binding to ACE2 throughconformational selection</strong> -
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The first step of SARS-CoV-2 infection involves the interaction between the trimeric viral spike protein () and the host angiotensin-converting enzyme 2 (2). The receptor binding domain () of adopts two conformations: open and closed, respectively, accessible and inaccessible to 2. Therefore, motions are suspected to affect 2 binding; yet a quantitative description of the underlying mechanism has been elusive. Here, using single-molecule approaches, we visualize opening and closing and probe the /2 interaction. Our results show that RBD dynamics affect 2 binding but not unbinding. The resulting modulation is quantitatively predicted by a conformational selection model in which each protomer behaves independently. Our work reveals a general molecular mechanism affecting binding affinity without altering binding strength, helping to understand coronavirus infection and immune evasion.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.15.585207v1" target="_blank">Modulation of SARS-CoV-2 spike binding to ACE2 throughconformational selection</a>
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<li><strong>Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition</strong> -
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SARS-CoV-2 infection triggers strong antibody response toward Nucleocapsid-Protein (NP), suggesting extracellular presence beyond its intra-virion RNA binding. Interestingly, NP was found to decorate infected and proximal uninfected cell-surfaces. Here, we propose a new mechanism through which extracellular NP on uninfected cells contributes to COVID-19 pathogenicity. We show that NP binds to cell-surface sulfated linear-glycosaminoglycans by spatial rearrangement of its RNA-binding sites facilitated by the flexible, positively charged, linker. Coating of uninfected lung-derived cells with purified NP attracted anti-NP-IgG from lung fluids and sera collected from COVID-19 patients. The magnitude of this immune recognition was significantly elevated in moderate compared to mild COVID-19 cases. Importantly, binding of anti-NP-IgG present in sera generated clusters that triggered C3b deposition by the classical complement pathway. Heparin analog enoxaparin outcompeted NP-binding, rescuing cells from anti-NP IgG-mediated complement deposition. Our findings unveil how extracellular NP may exacerbate COVID-19 tissue damage, and suggest leads for preventative therapy.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.17.585388v1" target="_blank">Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition</a>
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<li><strong>CORACLE (COVID-19 liteRAture CompiLEr): A platform for efficient tracking and extraction of SARS-CoV-2 and COVID-19 literature, with examples from post-COVID with respiratory involvement</strong> -
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Background: During COVID-19 pandemic there emerged a need to efficiently monitor and process large volumes of scientific literature on the subject. Currently, as the pandemic is winding down, the clinicians encountered a novel syndrome - Post-acute Sequelae of COVID-19 (PASC) - that affects over 10% of those who contract SARS-CoV-2 and presents a significant and growing challenge in the medical field. The continuous influx of new research publications underscores a critical need for efficient tools for navigating the literature. Objectives: We aimed to develop an application which will allow monitoring and categorizing COVID-19-related literature through building publication networks and medical subject headings (MeSH) maps to be able to quickly identify key publications and publication networks. Methods: We introduce CORACLE (COVID-19 liteRAture CompiLEr), an innovative web application designed for the analysis of COVID-19-related scientific articles and the identification of research trends. CORACLE features three primary interfaces: The "Search" interface, which displays research trends and citation links; the "Citation Map" interface, allowing users to create tailored citation networks from PubMed Identifiers (PMIDs) to uncover common references among selected articles; and the "MeSH" interface, highlighting current MeSH trends and associations between MeSH terms. Results: Our web application, CORACLE, leverages regularly updated PubMed data to aggregate and categorize the extensive literature on COVID-19 and PASC, aiding in the identification of relevant research publication hubs. Using lung function in PASC patients as a search example, we demonstrate how to identify and visualize the interactions between the relevant publications. Conclusion: CORACLE proves to be an effective tool for the extraction and analysis of literature. Its functionalities, including the MeSH trends and customizable citation mapping, facilitate the discovery of relevant information and emerging trends in COVID-19 and PASC research.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.18.584627v1" target="_blank">CORACLE (COVID-19 liteRAture CompiLEr): A platform for efficient tracking and extraction of SARS-CoV-2 and COVID-19 literature, with examples from post-COVID with respiratory involvement</a>
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<li><strong>Young Parents’ Experiences of Pregnancy and Parenting during the COVID-19 Pandemic: A qualitative study in the United Kingdom</strong> -
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Young parents (aged 16-24 years) in the perinatal period may be at an increased risk of poor mental health during the COVID-19 pandemic, due to multiple risk factors, including social and economic instability. COVID-19 related restrictions had significant implications for the delivery of some perinatal care services and other support structures for young parents. Investigating young parents’ experiences during the COVID-19 pandemic, including their perceived challenges and needs, is important to inform good practice and provide appropriate support for young parents. Qualitative interviews were conducted with young parents (n=21) during the COVID-19 pandemic in the United Kingdom from February – May 2021. Data were analysed using thematic analysis. Three key themes were identified to describe parents’ experiences during the COVID-19 pandemic. Parents reported specific COVID-19 related anxieties and stressors, including worries around contracting the virus and increased feelings of distress due to uncertainty created by the implications of the pandemic. Parents described feeling alone both at home and during antenatal appointments and highlighted the absence of social support as a major area of concern. Also, parents felt their perinatal care had been disrupted by the pandemic and experienced difficulties accessing care online or over the phone. This study highlights the potential impact of COVID-19 on young parents, including on their mental wellbeing and the perinatal support they were able to access during the pandemic. Insights from this study could inform the support and services offered to families during future pandemics. Specifically, the findings underlie the importance of (a) supporting both parents during perinatal appointments, (b) providing parents with early mental health support and (c) finding ways to facilitate communication pathways between professionals and parents.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/h3b6y/" target="_blank">Young Parents’ Experiences of Pregnancy and Parenting during the COVID-19 Pandemic: A qualitative study in the United Kingdom</a>
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<li><strong>Demographic and health factors associated with pandemic anxiety in the context of COVID-19</strong> -
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Objectives The mental health consequences of COVID-19 are predicted to have a disproportionate impact on certain groups. We aimed to develop a brief measure, the Pandemic Anxiety Scale, to capture the specific aspects of the pandemic that are provoking anxiety, and explore how these vary by health and demographic factors. Design Data were from a convenience sample of parents (N=4,793) and adolescents (N=698) recruited in the first 6 weeks of lockdown. Methods Factor analytic and IRT methods were used to validate the new measure in both parent and adolescent samples. Associations between scores on the new measure and age, gender, household income, and physical health status were explored using structural equation modelling (SEM). Results Two factors were identified in both samples: disease-anxiety (e.g. catching, transmitting the virus) and consequence anxiety (e.g. impact on economic prospects), and unique associations with health and demographic factors were observed. Conclusions Anxieties due to the COVID-19 are multifaceted, and the PAS is a short, reliable and valid measure of these concerns. These anxieties are differentially associated with demographic, social and health factors, which should be considered when developing strategies to mitigate the mental health impact of the pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/2eksd/" target="_blank">Demographic and health factors associated with pandemic anxiety in the context of COVID-19</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>Valacyclovir Plus Celecoxib for Post-Acute Sequelae of SARS-CoV-2</strong> - <b>Conditions</b>: PASC Post Acute Sequelae of COVID 19; Long COVID <br/><b>Interventions</b>: Drug: 1500 Valacyclovir 200 Celecoxib; Drug: 750 Valacyclovir 200 Celecoxib; Drug: Placebo <br/><b>Sponsors</b>: Bateman Horne Center <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Supervised Computerized Active Program for People With Post-COVID Syndrome (SuperCAP Study)</strong> - <b>Conditions</b>: Post-COVID Condition <br/><b>Interventions</b>: Device: SuperCAP Program <br/><b>Sponsors</b>: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia; Institut de Recerca de la SIDA IrsiCaixa; Germans Trias i Pujol Hospital <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Utilizing Novel Blood RNA Biomarkers as a Diagnostic Tool in the Identification of Long COVID-19</strong> - <b>Conditions</b>: Long COVID <br/><b>Interventions</b>: Diagnostic Test: RNA Biomarker Blood Test <br/><b>Sponsors</b>: MaxWell Clinic, PLC <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes</strong> - <b>Conditions</b>: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome <br/><b>Interventions</b>: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT) <br/><b>Sponsors</b>: Princess Nourah Bint Abdulrahman University <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC Platform Protocol</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SVF for Treating Pulmonary Fibrosis Post COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis <br/><b>Interventions</b>: Biological: Autologous adipose-derived SVF IV administration <br/><b>Sponsors</b>: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)</strong> - <b>Conditions</b>: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>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>Understanding Adaptive Immune Response After COVID-19 Vaccination Boosters to Improve Vaccination Strategies in Vulnerable Groups.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Analisys of cellular response and humoral response to SARS-CoV-2 vaccine booster doses <br/><b>Sponsors</b>: IRCCS Sacro Cuore Don Calabria di Negrar <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>COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator) <br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC <br/><b>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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Supporting underrepresented students in health sciences: a fuzzy cognitive mapping approach to program evaluation</strong> - CONCLUSIONS: The findings from a multipronged analysis of mapping data demonstrate the value of this innovative approach to the field, especially when looking to incorporate student voices.</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>An ascidian Polycarpa aurata-derived pan-inhibitor against coronaviruses targeting M<sup>pro</sup></strong> - Coronaviruses (CoVs) are responsible for a wide range of illnesses in both animals and human. The main protease (M^(pro)) of CoVs is an attractive drug target, owing its critical and highly conserved role in viral replication. Here, we developed and refined an enzymatic technique to identify putative M^(pro) inhibitors from 189 marine chemicals and 46 terrestrial natural products. The IC(50) values of Polycarpine (1a), a marine natural substance we studied and synthesized, are 30.0 ± 2.5 nM for…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SARS-CoV-2 Orf6 is positioned in the nuclear pore complex by Rae1 to control nucleo-cytoplasmic transport</strong> - The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) accessory protein Orf6 works as an interferon antagonist, in part, by inhibiting the nuclear import activated p-STAT1, an activator of interferon-stimulated genes, and the export of the poly(A) RNA. Insight into the transport regulatory function of Orf6 has come from the observation that Orf6 binds to the nuclear pore complex (NPC) components Rae1 and Nup98. To gain further insight into the mechanism of Orf6-mediated transport…</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 retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients</strong> - The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities,…</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>Yemazhui () ameliorates lipopolysaccharide-induced acute lung injury modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flora in rats</strong> - CONCLUSIONS: In summary, our findings revealed that HEL has a protective effect on LPS-induced ALI in rats, and its mechanism may be related to inhibiting TLR4/ NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.</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>Urinary cadmium concentration is associated with the severity and clinical outcomes of COVID-19: a bicenter observational cohort study</strong> - CONCLUSIONS: Urine cadmium concentration in the early course of COVID-19 could predict the severity and clinical outcomes of patients and was independently associated with the risk of severe COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Functional dissection of the spike glycoprotein S1 subunit and identification of cellular cofactors for regulation of swine acute diarrhea syndrome coronavirus entry</strong> - Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a novel porcine enteric coronavirus, and the broad interspecies infection of SADS-CoV poses a potential threat to human health. This study provides experimental evidence to dissect the roles of distinct domains within the SADS-CoV spike S1 subunit in cellular entry. Specifically, we expressed the S1 and its subdomains, S1^(A) and S1^(B). Cell binding and invasion inhibition assays revealed a preference for the S1^(B) subdomain in binding to…</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>Health-promoting benefits of lentils: Anti-inflammatory and anti-microbial effects</strong> - This paper describes how lentils (Lens culinaris species) can positively affect health by reducing inflammation, providing antioxidants, and displaying antimicrobial properties. Lentils are rich in proteins, essential amino acids, minerals, and fibers, making them a valuable source of nutrition, particularly in low and middle-income countries. Lentils have many health benefits, including positive effects on diabetes management, support for cardiovascular health, and antioxidative properties. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Happy Hour: The association between trait hedonic capacity and motivation to drink alcohol</strong> - The (over)consumption of alcohol and other addictive substances is often conceptualized as a problem of low self-control (i.e., people’s inability to inhibit unwanted impulses). According to that view, people drink because they cannot resist. In the present studies, we approached this from a different perspective and tested whether alcohol consumption might also be a problem of low hedonic capacity (i.e., people’s inability to experience pleasure and relaxation, often due to intrusive thoughts)….</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>Compound C inhibits the replication of feline coronavirus</strong> - Feline Coronavirus (FCoV) is a viral pathogen of cats and a highly contagious virus. Cats in a cattery can be infected by up to 100%, and even household cats are infected by 20-60%. Some strains of FCoV are known to induce a fatal disease in cats named Feline Infectious Peritonitis (FIP). However, no effective treatments are available. We demonstrated that compound C (dorsomorphin) can potentially inhibit feline coronavirus replication. Compound C treatment decreased the FCoV-induced plaque…</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>Hyperoside inhibits EHV-8 infection via alleviating oxidative stress and IFN production through activating JNK/Keap1/Nrf2/HO-1 signaling pathways</strong> - Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of polyphenols against complications of COVID-19: current evidence and potential efficacy</strong> - The COVID-19 pandemic that started in 2019 and resulted in significant morbidity and mortality continues to be a significant global health challenge, characterized by inflammation, oxidative stress, and immune system dysfunction.. Developing therapies for preventing or treating COVID-19 remains an important goal for pharmacology and drug development research. Polyphenols are effective against various viral infections and can be extracted and isolated from plants without losing their therapeutic…</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 Poly Aptamer Encoded DNA Nanocatcher Informs Efficient Virus Trapping</strong> - Broad-spectrum antiviral platforms are always desired but still lack the ability to cope with the threats to global public health. Herein, we develop a poly aptamer encoded DNA nanocatcher platform that can trap entire virus particles to inhibit infection with a broad antiviral spectrum. Ultralong single-stranded DNA (ssDNA) containing repeated aptamers was synthesized as the scaffold of a nanocatcher via a biocatalytic process, wherein mineralization of magnesium pyrophosphate on the ssDNA…</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>Unveiling the Antiviral Capabilities of Targeting Human Dihydroorotate Dehydrogenase against SARS-CoV-2</strong> - The urgent need for effective treatments against emerging viral diseases, driven by drug-resistant strains and new viral variants, remains critical. We focus on inhibiting the human dihydroorotate dehydrogenase (HsDHODH), one of the main enzymes responsible for pyrimidine nucleotide synthesis. This strategy could impede viral replication without provoking resistance. We evaluated naphthoquinone fragments, discovering potent HsDHODH inhibition with IC(50) ranging from 48 to 684 nM, and promising…</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>Targeting G9a translational mechanism of SARS-CoV-2 pathogenesis for multifaceted therapeutics of COVID-19 and its sequalae</strong> - By largely unknown mechanism(s), SARS-CoV-2 hijacks the host translation apparatus to promote COVID-19 pathogenesis. We report that the histone methyltransferase G9a noncanonically regulates viral hijacking of the translation machinery to bring about COVID-19 symptoms of hyperinflammation, lymphopenia, and blood coagulation. Chemoproteomic analysis of COVID-19 patient peripheral mononuclear blood cells (PBMC) identified enhanced interactions between SARS-CoV-2-upregulated G9a and distinct…</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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