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174 lines
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<title>14 February, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Everyday Emotional Functioning in COVID-19 Lockdowns</strong> -
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<div>
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Throughout the COVID-19 pandemic, policy makers have tried to balance the effectiveness of lockdowns (i.e., stay-at-home orders) with their potential mental health costs. Yet, several years into the pandemic, policy makers lack solid evidence about the toll of lockdowns on daily emotional functioning. Using data from two intensive longitudinal studies conducted in Australia in 2021, we compared the intensity, persistence, and regulation of emotions on days in and out of lockdown. Participants (N = 441, observations = 14,511) completed a 7-day study either entirely in lockdown, entirely out of lockdown, or both in and out of lockdown. We assessed emotions in general (Dataset 1) and in the context of social interactions (Dataset 2). Lockdowns took an emotional toll, but this toll was relatively mild: In lockdown, people experienced slightly more negative and less positive emotion; returned to a mildly negative emotional state more quickly; and used low-effort emotion regulation strategies (i.e., distraction). There are three interpretations for our findings, which are not mutually exclusive. First, people may be relatively resilient to the emotional challenges posed by repeated lockdowns. Second, lockdowns may not compound the emotional challenges of the pandemic. Third, because we found effects even in a mostly childless and well-educated sample, lockdowns may take a greater emotional toll in samples with less pandemic privilege. Indeed, the high level of pandemic privilege of our sample limits the generalizability of our findings (e.g., to people with caregiving roles).
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/hxatc/" target="_blank">Everyday Emotional Functioning in COVID-19 Lockdowns</a>
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<li><strong>Two dimensions of chemical variation of the human microbiome across body sites and in COVID-19 patients</strong> -
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<div>
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A better understanding of dysbiosis is a major goal of human microbiome studies, but more knowledge about chemical effects on microbial communities is needed. Oxidation-reduction and hydration-dehydration reactions are chemical processes that are important for physiological functions and, it is hypothesized here, may also influence the elemental composition of microbial proteins. Chemical metrics of biomolecules relevant to these processes are carbon oxidation state (ZC) and stoichiometric hydration state (nH2O). I calculated these metrics for protein sequences derived from microbial genomes (multiplied by 16S rRNA-based taxonomic abundances to obtain community reference proteomes), shotgun metagenomes, and metaproteomes. Metaproteomes of gut communities are reduced (i.e., have lower ZC) compared to oral communities. In contrast, community reference proteomes have lower nH2O in gut compared to nasal, skin, and oral communities, and metagenomes for gut and oral communities exhibit the same trend. The chemical differences for metaproteomes may be explained by physiological adjustment of protein expression levels to anaerobic, reducing conditions in the gut, whereas metagenomes and reference proteomes may reflect evolutionary adaptation to dehydrating conditions brought on by intestinal absorption of water. Community reference proteomes, metagenome-assembled genomes (MAGs), and metaproteomes compiled from various studies yield a common trend of more reduced proteins in gut communities of COVID-19 patients compared to controls. These chemical differences imply more reducing conditions in the guts of COVID-19 patients, a finding that contrasts with oxidative conditions that have been previously associated with dysbiosis in inflammatory bowel disease and HIV infection. These results reveal how the human microbiome is shaped by multiple chemical factors over a range of timescales and suggest a new strategy for using multi-omics data to infer changes in gut redox conditions in COVID-19 patients.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.12.528246v1" target="_blank">Two dimensions of chemical variation of the human microbiome across body sites and in COVID-19 patients</a>
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</div></li>
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<li><strong>Susceptibility to misinformation: a study of climate change, Covid-19, and artificial intelligence</strong> -
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This study explores whether susceptibility to misinformation is context dependent. We conduct a survey experiment in which subjects had to rate the reliability of several statements in the fields of climate change, Covid-19, and artificial intelligence. There is some evidence for a monological belief system, i.e., being susceptible to one statement containing misinformation is correlated with falling to other false news stories, in all three contexts. The main findings to explain the susceptibility to misinformation can be summarized as follows: trust in social networks is positively associated with falling for misinformation in all contexts. There are also several context-related differences: Individuals are less likely to be susceptible to misinformation in the contexts of climate change and Covid-19 if they have a higher risk perception, tend to take a second look at a problem (i.e., willingness to think deliberately), update their prior beliefs to new evidence (actively open-minded thinking), and trust in science and mass media. Within the context of artificial intelligence, being less prone to conspiracy theories in general and lower subjective knowledge helps not to be susceptible to misinformation.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/x8efq/" target="_blank">Susceptibility to misinformation: a study of climate change, Covid-19, and artificial intelligence</a>
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</div></li>
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<li><strong>The intention to be vaccinated against COVID-19: Stated preferences before vaccines were available</strong> -
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<div>
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The goal of this note is to better understand determinants that can explain the willingness to vaccinate against COVID-19. For this purpose, we conduct a survey in Germany in which we ask ourselves whether this “time is different” from the willingness to be vaccinated against infection by influenza viruses. Our sample does not only comprise students with and without healthcare background, we also analyze a notable amount of healthcare professionals. We find that healthcare professionals exhibit a considerably greater willingness to vaccinate against flu than healthcare and non-healthcare students. In contrast, the willingness to vaccinate against COVID-19 is quite similar among the populations. In both contexts, COVID-19 and flu, trust (e.g. media, activities of the government) seems to play a central role in the decision whether to vaccinate or not.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/wh268/" target="_blank">The intention to be vaccinated against COVID-19: Stated preferences before vaccines were available</a>
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</div></li>
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<li><strong>Positing changes in neutralizing antibody activity for SARS-CoV-2 XBB.1.5 using in silico protein modeling</strong> -
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<div>
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The SARS-CoV-2 variant XBB.1.5 is of concern as it has high transmissibility. XBB.1.5 currently accounts for upwards of 30% of new infections in the United States. One year after our group published the predicted structure of the Omicron (B.1.1.529) variant’s receptor binding domain and antibody binding affinity, we return to investigate the new mutations seen in XBB.1.5. Using in silico modeling approaches against newer neutralizing antibodies that are shown effective against B.1.1.529, we posit the immune consequences of XBB.1.5’s mutations and show that there is no statistically significant difference in overall antibody evasion when comparing to the B.1.1.529, BJ.1, and BM.1.1.1 variants. However, specific noticeable hints of neutralizing activity changes were seen due to particular amino acid changes of interest in the newer variants.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528025v1" target="_blank">Positing changes in neutralizing antibody activity for SARS-CoV-2 XBB.1.5 using in silico protein modeling</a>
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</div></li>
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<li><strong>Olivar: fully automated and variant aware primer design for multiplex tiled amplicon sequencing of pathogen genomes</strong> -
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<div>
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Tiled amplicon sequencing has served as an essential tool for tracking the spread and evolution of SARS-CoV-2 in real-time directly from environmental and clinical samples. Over 14 million SARS-CoV-2 genomes are now available on GISAID, most sequenced and assembled via tiled amplicon sequencing. While computational tools for tiled amplicon design exist, they require downstream manual optimization both computationally and experimentally, which is slow, laborious, and costly. Here, we present Olivar, the first open-source computational tool capable of fully automating the design of tiled amplicons by integrating SNPs, non-specific amplification, etc. into a “risk score” for each single nucleotide of the target genome. Oli- var evaluates thousands sets of possible tiled amplicons and minimizes primer dimer in parallel. In a direct in-silico com- parison with PrimalScheme, we show that Olivar has fewer SNPs overlapping with primers and predicted PCR byproducts. We also compared Olivar head-to-head with ARTIC v4.1, the most widely used tiled amplicons for SARS-CoV-2 sequencing. We next tested Olivar on real wastewater samples and found that our automated approach had up to 3-fold higher map- ping rates compared to ARTIC v4.1 while retaining similar coverage. To the best of our knowledge, Olivar represents the first open-source, fully automated design tool that simultaneously evaluates and optimizes risks of known primer design issues for robust tiled amplicon sequencing. Olivar is available as a web application at https://olivar.rice.edu/. Olivar can also be installed locally as a command line tool with Bioconda. Source code, installation guide and usage are available at https: //gitlab.com/treangenlab/olivar.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.11.528155v1" target="_blank">Olivar: fully automated and variant aware primer design for multiplex tiled amplicon sequencing of pathogen genomes</a>
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</div></li>
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<li><strong>Nuclear export inhibitor Selinexor targeting XPO1 enhances coronavirus replication.</strong> -
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<div>
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Nucleocytoplasmic transport of proteins using XPO1 (exportin 1) plays a vital role in cell proliferation and survival. Many viruses also exploit this pathway to promote infection and replication. Thus, inhibiting XPO1-mediated nuclear export with selective inhibitors activates multiple antiviral and anti-inflammatory pathways. The XPO1 inhibitor, Selinexor, is an FDA-approved anticancer drug predicted to have antiviral function against many viruses, including SARS-CoV-2. Unexpectedly, we observed that pretreatment of cultured human cells with Selinexor actually enhanced protein expression and replication of coronaviruses, including SARS-CoV-2. Knockdown of cellular XPO1 protein expression significantly enhanced the replication of coronaviruses in human cells. We further demonstrate that Selinexor treatment reduced the formation of unique cytoplasmic antiviral granules that include RNA helicase DHX9 in the virus-infected cells. These results, for the first time, show that the anti-cancer drug Selinexor enhances the replication of coronaviruses in human cells in vitro and thus should be further explored in vivo for the potential impact on the dual use for anticancer and antiviral therapy.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.09.527884v1" target="_blank">Nuclear export inhibitor Selinexor targeting XPO1 enhances coronavirus replication.</a>
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<li><strong>Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</strong> -
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<div>
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Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a common post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1-deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings suggest that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis and biology of SARS-CoV-2 infection.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527147v1" target="_blank">Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease</a>
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</div></li>
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<li><strong>LINE1-mediated reverse transcription and genomic integration of SARS-CoV-2 mRNA detected in virus-infected but not in viral mRNA-transfected cells</strong> -
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<div>
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SARS-CoV-2 sequences can be reverse-transcribed and integrated into the genomes of virus-infected cells by a LINE1-mediated retrotransposition mechanism. Whole genome sequencing (WGS) methods detected retrotransposed SARS-CoV-2 subgenomic sequences in virus-infected cells overexpressing LINE1, while an enrichment method (TagMap) identified retrotranspositions in cells that did not overexpress LINE1. LINE1 overexpression increased retrotranspositions about 1,000-fold as compared to non-overexpressing cells. Nanopore WGS can directly recover retrotransposed viral and flanking host sequences but its sensitivity depends on the depth of sequencing (a typical 20-fold sequencing depth would only examine 10 diploid cell equivalents). In contrast, TagMap enriches for the host-virus junctions and can interrogate up to 20,000 cells and is able to detect rare viral retrotranspositions in LINE1 non-overexpressing cells. Although Nanopore WGS is 10 - 20-fold more sensitive per tested cell, TagMap can interrogate 1,000 - 2,000-fold more cells and therefore can identify infrequent retrotranspositions. When comparing SARS-CoV-2 infection and viral nucleocapsid mRNA transfection by TagMap, retrotransposed SARS-CoV-2 sequences were only detected in infected but not in transfected cells. Retrotransposition in virus-infected in contrast to transfected cells may be facilitated because virus infection in contrast to viral RNA transfection results in significantly higher viral RNA levels and stimulates LINE1-expression which causes cellular stress.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527906v1" target="_blank">LINE1-mediated reverse transcription and genomic integration of SARS-CoV-2 mRNA detected in virus-infected but not in viral mRNA-transfected cells</a>
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<li><strong>Regulatory T Cell-like Response to SARS-CoV-2 in Jamaican Fruit Bats Transduced with Human ACE2</strong> -
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<div>
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Insectivorous Old World horseshoe bats (Rhinolophus spp.) are the likely source of the ancestral SARS-CoV-2 prior to its spillover into humans and causing the COVID-19 pandemic. Natural coronavirus infections of bats appear to be principally confined to the intestines, suggesting fecal-oral transmission; however, little is known about the biology of SARS-related coronaviruses in bats. Previous experimental challenges of Egyptian fruit bats (Rousettus aegyptiacus) resulted in limited infection restricted to the respiratory tract, whereas insectivorous North American big brown bats (Eptesicus fuscus) showed no evidence of infection. In the present study, we challenged Jamaican fruit bats (Artibeus jamaicensis) with SARS-CoV-2 to determine their susceptibility. Infection was confined to the intestine for only a few days with prominent viral nucleocapsid antigen in epithelial cells, and mononuclear cells of the lamina propria and Peyers patches, but with no evidence of infection of other tissues; none of the bats showed visible signs of disease or seroconverted. Expression levels of ACE2 were low in the lungs, which may account for the lack of pulmonary infection. Bats were then intranasally inoculated with a replication-defective adenovirus encoding human ACE2 and 5 days later challenged with SARS-CoV-2. Viral antigen was prominent in lungs for up to 14 days, with loss of pulmonary cellularity during this time; however, the bats did not exhibit weight loss or visible signs of disease. From day 7, bats had low to moderate IgG antibody titers to spike protein by ELISA, and one bat on day 10 had low-titer neutralizing antibodies by a VSV pseudotyped virus assay. CD4+ helper T cells became activated upon ex vivo recall stimulation with SARS-CoV-2 nucleocapsid peptides and exhibited elevated mRNA expression of the regulatory T cell cytokines interleukin-10 and transforming growth factor beta, which may have limited inflammatory pathology. Collectively, these data show that Jamaican fruit bats are of low susceptibility to SARS-CoV-2 but that expression of human ACE2 in their lungs leads to robust infection and an adaptive immune response with low-titer antibodies and a regulatory T cell-like response that may explain the lack of prominent inflammation in the lungs. This model will allow for insights of how SARS-CoV-2 infects bats and how bat innate and adaptive immune responses engage the virus without overt clinical disease.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.13.528205v1" target="_blank">Regulatory T Cell-like Response to SARS-CoV-2 in Jamaican Fruit Bats Transduced with Human ACE2</a>
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<li><strong>The disordered N-terminal tail of SARS CoV-2 Nucleocapsid protein forms a dynamic complex with RNA</strong> -
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The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Characterizing the mechanisms controlling nucleic acid binding is a key step in understanding how condensation is realized. Here, we focus on the role of the RNA Binding Domain (RBD) and its flanking disordered N-Terminal Domain (NTD) tail, using single-molecule Forster Resonance Energy Transfer and coarse-grained simulations. We quantified contact site size and binding affinity for nucleic acids and concomitant conformational changes occurring in the disordered region. We found that the disordered NTD increases the affinity of the RBD for RNA by about 50-fold. Binding of both nonspecific and specific RNA results in a modulation of the tail configurations, which respond in an RNA length-dependent manner. Not only does the disordered NTD increase affinity for RNA, but mutations that occur in the Omicron variant modulate the interactions, indicating a functional role of the disordered tail. Finally, we found that the NTD-RBD preferentially interacts with single-stranded RNA and that the resulting protein:RNA complexes are flexible and dynamic. We speculate that this mechanism of interaction enables the Nucleocapsid protein to search the viral genome for and bind to high-affinity motifs.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527914v1" target="_blank">The disordered N-terminal tail of SARS CoV-2 Nucleocapsid protein forms a dynamic complex with RNA</a>
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<li><strong>Single-virus fusion measurements reveal multiple mechanistically equivalent pathways for SARS-CoV-2 entry</strong> -
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SARS-CoV-2 binds to cell-surface receptors and is activated for membrane fusion and cell entry via proteolytic cleavage. Phenomenological data have shown that SARS-CoV-2 can be activated for entry at either the cell surface or in endosomes, but the relative roles in different cell types and mechanisms of entry have been debated. Here we use single-virus fusion experiments and exogenously controlled proteases to probe activation directly. We find that plasma membrane and an appropriate protease are sufficient to support SARS-CoV-2 pseudovirus fusion. Furthermore, fusion kinetics of SARS-CoV-2 pseudoviruses are indistinguishable no matter which of a broad range of proteases was used to activate the virus. This suggests that fusion mechanism is insensitive to protease identity or even whether activation occurs before or after receptor binding. These data support a model for opportunistic fusion by SARS-CoV-2, where subcellular location of entry likely depends on the differential activity of airway, cell-surface, and endosomal proteases, but all support infection. Inhibiting any single host protease may thus reduce infection in some cells but may be less clinically robust.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2021.05.04.442634v3" target="_blank">Single-virus fusion measurements reveal multiple mechanistically equivalent pathways for SARS-CoV-2 entry</a>
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<li><strong>Don’t say it’s over: the perceived epidemic stage, COVID risk perception and preventive behaviour</strong> -
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The risks for people during the epidemic are evolving. For COVID-19 pandemic one important feature was its multiwave pattern, where, within each wave, the pandemic dynamic could be described as the curve. This study aimed to explore how people’s perceptions of such a pandemic process associates with the risk perceptions and the preventive behaviour. A sample of 1,343 university students in the beginning of COVID-19 pandemic have assessed the pandemic stage, perceived risks, mental health and trust to different bodies in regard to pandemic. They also reported their involvement in the COVID topic and a wide range of implemented behaviour. The study participants differed in their perception of the pandemic stage despite being in the same environment. The belief that the curve pick is left behind was associated with the less perceived risk and decrease in preventive behaviour implementation, while there was no difference in the perception of risks or behaviour between belief in living the period in the epidemic peak or the beginning of the wave. The lack of COVID involvement, distrust to authorities and official COVID information were associated with the less perceived risk and preventive behaviour. Mental health characteristics were significantly associated with the social preventive behaviours - the higher depression level was the predictor of the decreasing of communication with other people while the anxiety was the predictor of more risky behaviour due to increase in face-to-face communication. Overall the perception that the epidemic wave is on its final stage could be an independent predictor of more risky behaviour. Communication of the epidemic dynamic should be provided with extreme caution.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/pzw3f/" target="_blank">Don’t say it’s over: the perceived epidemic stage, COVID risk perception and preventive behaviour</a>
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<li><strong>LEA: Latent Eigenvalue Analysis in application to high-throughput phenotypic profiling</strong> -
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Understanding the phenotypic characteristics of cells in culture and detecting perturbations introduced by drug stimulation is of great importance for biomedical research. However, a thorough and comprehensive analysis of phenotypic heterogeneity is challenged by the complex nature of cell-level data. Here, we propose a novel Latent Eigenvalue Analysis (LEA) framework and apply it to high-throughput phenotypic profiling with single-cell and single-organelle granularity. Using the publicly available SARS-CoV-2 datasets stained with the multiplexed fluorescent cell-painting protocol, we demonstrate the power of the LEA approach in the investigation of phenotypic changes induced by more than 1800 drug compounds. As a result, LEA achieves a robust quantification of phenotypic changes introduced by drug treatment. Moreover, this quantification can be biologically supported by simulating clearly observable phenotypic transitions in a broad spectrum of use cases. Lastly, we describe the LEA pipeline in detail and illustrate the application to further use cases in the biomedical image domain, underlining the domain-agnostic facet of our methodological approach. In conclusion, LEA represents a new and broadly applicable approach for quantitative and interpretable analysis of biomedical image data. Our code and video demos are publicly available via https://github.com/CTPLab/LEA.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528026v1" target="_blank">LEA: Latent Eigenvalue Analysis in application to high-throughput phenotypic profiling</a>
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<li><strong>Patterns of testing in the extensive Danish national SARS-CoV-2 test set-up</strong> -
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Background: The Danish national SARS-CoV-2 mass test system was among the most ambitious worldwide. We describe its set-up and analyse differences in patterns of testing per demography and time period in relation to the three waves of SARS-CoV-2 transmission in Denmark. Methods: We included all reported PCR- and rapid antigen-tests performed between 27 February 2020 and 10 March 2022 among all residents aged 2 years or above. Descriptive statistics and Poisson regression models were used to analyse characteristics of individuals tested for SARS-CoV-2 using a national cohort study design. Results: A total of 63.7 million PCR-tests and 60.0 million antigen-tests were performed in the study period, testing 91.1% and 79.2% of the Danish population at least once by PCR or antigen, respectively. Female sex, younger age, Danish heritage and living in the capital area were all factors positively associated with the frequency of PCR-testing. The association between COVID-19 vaccination and PCR-testing changed from negative to positive over time. Conclusion: We provide details of the widely available, free-of-charge, national SARS-CoV-2 test system, which served to identify infected individuals, assist isolation of infectious individuals and contact tracing, and thereby mitigating the spread of SARS-CoV-2 in the Danish population. The test system was utilized by nearly the entire population at least once, and widely accepted across different demographic groups. However, demographic differences in the test uptake did exist and should be considered in order not to cause biases in studies related to SARS-CoV-2, e.g., studies of transmission and vaccine effectiveness.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.06.23285556v2" target="_blank">Patterns of testing in the extensive Danish national SARS-CoV-2 test set-up</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>MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: Manzi Guben granules<br/><b>Sponsors</b>: Second Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital of Zhejiang Chinese Medical University; Hangzhou Hospital of Traditional Chinese Medicine; Suzhou Hospital of Traditional Chinese Medicine<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>Phase Ⅰ Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>: Wuhan BravoVax Co., Ltd.; National University Hospital, Singapore; Shanghai BravoBio Co., 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>Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Pilates Exercises<br/><b>Sponsor</b>: Michele de Aguiar Zacaria<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>Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Persuasive Appeal<br/><b>Sponsor</b>: University of Calgary<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>Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AZD 1222<br/><b>Sponsors</b>: Botswana Harvard AIDS Institute Partnership; AstraZeneca; Botswana Ministry of Health<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>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>: Cairo University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: GS-5245; Drug: GS-5245 Placebo<br/><b>Sponsor</b>: Gilead Sciences<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: HH-120 nasal spray; Drug: Placebo Comparator<br/><b>Sponsor</b>: Huahui Health<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>Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Double-Stranded RNA sodium salt; 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>Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: VV116+SOC; Drug: SOC<br/><b>Sponsor</b>: Chengdu Zenitar Biomedical Technology Co., Ltd<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>Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: STI-1558; Drug: STI-1558 placebo<br/><b>Sponsor</b>: Zhejiang ACEA Pharmaceutical Co. 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>Pirfenidone in Adult Hospitalized Patients With COVID-19</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Pirfenidone Oral Product; Drug: Pirfenidone placebo<br/><b>Sponsor</b>: Capital Medical University<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 and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19</strong> - <b>Condition</b>: Long COVID-19<br/><b>Intervention</b>: Biological: UC-MSCs<br/><b>Sponsor</b>: Shanghai East Hospital<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>CONFIDENCE: A Pilot Randomized Control Trial With Waitlist Condition to Test a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents</strong> - <b>Condition</b>: COVID-19 Vaccination<br/><b>Intervention</b>: Behavioral: CONFIDENCE<br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC; Baystate Health<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 Effectiveness of a Health Education Intervention to Reduce Anxiety in Quarantined COVID-19 Patients</strong> - <b>Condition</b>: Health Education, COVID-19, Quarantine, Anxiety, Pandemic<br/><b>Intervention</b>: Other: health education intervention<br/><b>Sponsor</b>: University of Monastir<br/><b>Completed</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>Remdesivir Use in Low Weight, Premature, and Renally Impaired Infants With SARS-CoV-2 Infection in Sheikh Khalifa Medical City, UAE: Case Series</strong> - Remdesivir possesses in vitro inhibitory effect against severe acute respiratory syndrome coronavirus 2 and the Middle East respiratory syndrome. It works by inhibiting severe acute respiratory syndrome coronavirus 2 RNA-dependent RNA polymerase that is essential for viral replication. Remdesivir is approved by Food and Drug Administration for treating COVID-19 in hospitalized adult and pediatric patients aged 28 days and more and weighing 3 kg and more. This case series is describing two cases…</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>Can Internet penetration curb the spread of infectious diseases among regions?-Analysis based on spatial spillover perspective</strong> - Based on the outbreak of COVID-19, this paper empirically studied the impact of internet penetration on the incidence of class A and B infectious diseases among regions in spatial Dubin model, by using health panel data from 31 provinces in China from 2009 to 2018. The findings showed that: (1) The regional spillover effect of incidence of class A and B infectious diseases was significantly positive, and that is most obvious in the central regions. (2) Internet penetration not only has a…</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 comprehensive survey of coronaviral main protease active site diversity in 3D: Identifying and analyzing drug discovery targets in search of broad specificity inhibitors for the next coronavirus pandemic</strong> - Although the rapid development of therapeutic responses to combat SARS-CoV-2 represents a great human achievement, it also demonstrates untapped potential for advanced pandemic preparedness. Cross-species efficacy against multiple human coronaviruses by the main protease (MPro) inhibitor nirmatrelvir raises the question of its breadth of inhibition and our preparedness against future coronaviral threats. Herein, we describe sequence and structural analyses of 346 unique MPro enzymes from all…</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>Stress adaptation signature into the functional units of spike, envelope, membrane protein and ssRNA of SARS-CoV-2</strong> - Pandemic coronavirus causes respiratory, enteric and sometimes neurological diseases. Proteome data of individual coronavirus strains were already reported. Here we investigated of SARS-CoV-2 ssRNA and protein of spike, envelope and membrane to determine stress adaptation profile. Thermodynamic properties, Physicochemical behaviour and, amino acid composition along with their RMSD value was analysed. Thermodynamic index of SARS-CoV2 spike, envelope and membrane ssRNA is unstable in higher…</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>Extensive blood transcriptome analysis reveals cellular signaling networks activated by circulating glycocalyx components reflecting vascular injury in COVID-19</strong> - CONCLUSIONS: Circulating glycocalyx components in COVID-19 have distinct biologic feedback effects on immune and endothelial cells and result in upregulation of key regulatory transcripts leading to further immune activation and more severe systemic inflammation. These consequences are most pronounced during the early hospital phase of COVID-19 before pulmonary failure develops. Elevated levels of circulating glycocalyx components may early identify patients at risk for microvascular injury 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>The evaluation of <em>in vitro</em> antichagasic and <em>anti</em>-SARS-CoV-2 potential of inclusion complexes of β- and methyl-β-cyclodextrin with naphthoquinone</strong> - The compound 3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione (IVS320) is a naphthoquinone with antifungal and antichagasic potential, which however has low aqueous solubility. To increase bioavailability, inclusion complexes with β-cyclodextrin (βCD) and methyl-β-cyclodextrin (MβCD) were prepared by physical mixture (PM), kneading (KN) and rotary evaporation (RE), and their in vitro anti-SARS-CoV-2 and antichagasic potential was assessed. The formation of inclusion complexes led 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>A review article on neuroprotective, immunomodulatory, and anti-inflammatory role of vitamin-D3 in elderly COVID-19 patients</strong> - Vitamin D3 is a secosteroid, broad-spectrum immunomodulatory, antioxidant, and anti-inflammatory hormone produced either by the internal subcutaneous pathway in the presence of ultraviolet B (UVB) rays or by the external pathway in the form of supplements. Vitamin D3 deficiency is a common and reversible contributor to mortality and morbidity among critically ill patients, including Coronavirus Disease 2019 (COVID-19) and other viral infections. The major functions of vitamin D3 are inhibiting…</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>Multigenerational effects of microplastic fragments derived from polyethylene terephthalate bottles on duckweed Lemna minor: Size-dependent effects of microplastics on photosynthesis</strong> - The 2019 global coronavirus disease pandemic has led to an increase in the demand for polyethylene terephthalate (PET) packaging. Although PET is one of the most recycled plastics, it is likely to enter the aquatic ecosystem. To date, the chronic effects of PET microplastics (MPs) on aquatic plants have not been fully understood. Therefore, this study aimed to investigate the adverse effects of PET MP fragments derived from PET bottles on the aquatic duckweed plant Lemna minor through a…</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>Structural basis of nirmatrelvir and ensitrelvir activity against naturally occurring polymorphisms of the SARS-CoV-2 Main Protease</strong> - SARS-CoV-2 is the causative agent of COVID-19. The main viral protease (M^(pro)) is an attractive target for antivirals. The clinically approved drug nirmatrelvir, and the clinical candidate ensitrelvir have so far showed great potential for treatment of viral infection. However, the broad use of antivirals is often associated with resistance generation. Herein, we enzymatically characterized 14 naturally occurring M^(pro) polymorphisms that are close to the binding site of these antivirals….</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>Comparison study of Beninese and Chinese herbal medicines in treating COVID-19</strong> - CONCLUSIONS: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.</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 influence of facemasks on communication in healthcare settings: a systematic review</strong> - CONCLUSIONS: Despite considerable complexity and heterogeneity in outcome measure, 93% (14 of 15) articles suggest respiratory protective equipment negatively affects speech understanding in normal hearing and hearing-impaired adults.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibitory Activity of <em>Saussurea costus</em> Extract against Bacteria, Candida, Herpes, and SARS-CoV-2</strong> - Medicinal herbs have long been utilized to treat various diseases or to relieve the symptoms of some ailments for extended periods. The present investigation demonstrates the phytochemical profile, molecular docking, anti-Candida activity, and anti-viral activity of the Saussurea costus acetic acid extract. GC-MS analysis of the extract revealed the presence of 69 chemical compounds. The chemical compounds were alkaloids (4%), terpenoids (79%), phenolic compounds (4%), hydrocarbons (7%), 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>3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors</strong> - The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2. Herein, we report the synthesis and study…</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>N</em>-Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents</strong> - New N-containing xanthone analogs of α-mangostin were synthesized via one-pot Smiles rearrangement. Using cesium carbonate in the presence of 2-chloroacetamide and catalytic potassium iodide, α-mangostin (1) was subsequently transformed in three steps to provide ether 2, amide 3, and amine 4 in good yields at an optimum ratio of 1:3:3, respectively. The evaluation of the biological activities of α-mangostin and analogs 2-4 was described. Amine 4 showed promising cytotoxicity against 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>Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells</strong> - Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety of wild Pu’er tea plants were two major ingredients responsible for the anti-influenza activity. As the COVID-19 outbreak is still lurking, developing safe and cost-effective therapeutics is an urgent need. This study aimed to evaluate the effects of these tea compounds on the infection of mouse hepatitis virus (MHV), a β-coronavirus serving as a surrogate for SARS-CoV. Treatment with strictinin (100 μM), but not…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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