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178 lines
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<title>18 January, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.</strong> -
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SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to Serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus’ evolution.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.15.524170v1" target="_blank">Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.</a>
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<li><strong>Natural evolution of SARS-CoV-2 variants in K18-ACE2 mice gives rise to more virulent virus and variant alleles associated with treatment resistance.</strong> -
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Background: The continuing COVID-19 pandemic is partially due to viral evolution decreasing vaccine and treatment efficacies. Predicting viral evolution is difficult. Others have found that serial infections of the original SARS-CoV-2 isolate in non transgenic mice is accompanied with selection of alleles (such as Spike 417N, 493H and 501Y) conferring adaptation and greater binding affinity for the murine ACE2 receptor, enhanced infectivity, and lethal phenotype in mice. We designed a study to investigate long-term viral evolution’s impact in K18-ACE2 mice with virus closer related to the Omicron sub-lineage. Methods: We serially infected SARS-CoV-2-naive mice with either the B.1.351 (Beta) or the B.1.617.2 (Delta) variant across twenty passages without selective pressures. We sequenced virus across passages, annotating variant alleles changing in frequency using published tools, tracking alleles suspected of decreasing vaccine/treatment efficacy. We evaluated virulence in animals infected with virus isolated at study completion and determined antibody neutralization sensitivity using sera from vaccinated individuals. Results and Conclusions: We observed variant alleles with documented roles in vaccine-elicited immunity evasion. This included the Omicron-associated mutation spike S371F that arose de-novo during our study. Passage 20 (P20) viruses were more virulent that their P0 counterpart with P20 Delta lineage being significantly more resistant to antibody neutralization. These developments occurred within two months of the study starting, suggesting that our model can rapidly emulate pandemic progression in mammals. While our model lacked selective pressures, such as pre-existing SARS-CoV-2 immunity, these conditions could readily be adapted. Such modeling could enable development of more evolution-resistant treatments.
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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/10.1101/2023.01.16.523994v1" target="_blank">Natural evolution of SARS-CoV-2 variants in K18-ACE2 mice gives rise to more virulent virus and variant alleles associated with treatment resistance.</a>
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</div></li>
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<li><strong>Exploration of the Link Between COVID-19 and Alcoholic Hepatitis from the Perspective of Bioinformatics and Systems Biology</strong> -
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Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been suggested to purpose threats to health of mankind. Alcoholic hepatitis (AH) is a life-threatening acute and chronic liver failure that takes place in sufferers who drink excessively. During the epidemic, AH has an increasing incidence of severe illness and mortality. However, for these two diseases, the intrinsic relationship of molecular pathogenesis, as well as common therapeutic strategies are still poorly understood. Methods: The transcriptome of the COVID-19 and AH has been compared to obtain the altered genes and hub genes were screened out through protein-protein interaction (PPI) network analysis. Via gene ontology (GO), pathway enrichment and transcription regulator analysis, a deeper appreciation of the interplay mechanism between hub genes were established. Results: With 181 common differentially expressed genes (DEGs) of AH and COVID-19 were obtained, 10 hub genes were captured. Follow-up studies located that these 10 genes typically mediated the diseases occurrence by regulating the activities of the immune system. Other results suggest that the common pathways of the two ailments are enriched in regulating the function of immune cells and the release of immune molecules. Conclusion: This study reveals the common pathogenesis of COVID-19 and AH and assist to discover necessary therapeutic targets to combat the ongoing pandemic induced via SARS-CoV-2 infection and acquire promising remedy strategies for the two diseases.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.14.524034v1" target="_blank">Exploration of the Link Between COVID-19 and Alcoholic Hepatitis from the Perspective of Bioinformatics and Systems Biology</a>
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<li><strong>Long-term cardiac symptoms following COVID-19: a systematic review and meta-analysis</strong> -
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Background There is growing body of literature on the long-term cardiac symptoms following COVID-19. We conducted a systematic review and meta analysis to synthesize and evaluate related evidence to inform clinical management and future studies. Methods We searched two preprint and seven peer reviewed article databases from January 1, 2020 to January 8, 2022 for studies investigating cardiac symptoms that persisted for at least 4 weeks among individuals who survived COVID-19. A customized Newcastle Ottawa scale was used to evaluate the quality of included studies. Random effects meta analyses were performed to estimate the proportion of symptoms with 95% confidence intervals (CI), and stratified analyses were conducted to quantify the proportion of symptoms by study characteristics and quality. Results A total of 101 studies describing 49 unique long-term cardiac symptoms met the inclusion criteria. Based on quality assessment, only 15.8% of the studies (n=16) were of high quality, and most studies scored poorly on sampling representativeness. The two most examined symptoms were chest pain and arrhythmia. Meta-analysis showed that the proportion of chest pain was 10.1% (95% CI: 6.4, 15.5) and arrhythmia was 9.8% (95% CI: 5.4, 17.2). Stratified analyses showed that studies with low-quality score, small sample size, unsystematic sampling method, and cross-sectional design were most likely to report high proportions of symptoms. For example, the proportion of chest pain was 21.3% (95% CI: 10.5, 38.5), 9.3% (95% CI: 6.0, 14.0), and 4.0% (95% CI: 1.3, 12.0) in studies with low, medium, and high-quality scores, respectively. Similar patterns were observed for other cardiac symptoms including hypertension, cardiac abnormalities, myocardial injury, thromboembolism, stroke, heart failure, coronary disease, and myocarditis. Discussion There is a wide spectrum of long-term cardiac symptoms following COVID-19. Findings of existing studies are strongly related to study quality, size and design, underscoring the need for high-quality epidemiologic studies to characterize these symptoms and understand their etiology.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.01.16.23284620v1" target="_blank">Long-term cardiac symptoms following COVID-19: a systematic review and meta-analysis</a>
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</div></li>
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<li><strong>Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a ‘National Plan’ to reopening</strong> -
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Background In mid-2021, widespread availability of COVID-19 vaccines with demonstrated impacts on transmission promised relief from the strict public health and social measures (PHSMs) imposed in many countries to limit spread and burden. We were asked to define vaccine coverage thresholds for transition through the stages of Australia9s 9National Plan9 to easing restrictions and reopening international borders. Methods Using available evidence of vaccine effectiveness against the then-circulating Delta variant, we used a mathematical model to determine vaccine coverage targets. The absence of any COVID-19 infections in many sub-national jurisdictions in Australia posed particular methodological challenges for modelling in this setting. We used a novel metric called Transmission Potential (TP) as a proxy measure of the population-level effective reproduction number. We estimated TP of the Delta variant under a range of PHSMs, test-trace-isolate-quarantine (TTIQ) efficiencies, vaccination coverage thresholds, and age-based vaccine allocation strategies. Findings We found that high coverage of vaccination across all age groups (≥ 70) combined with ongoing TTIQ and minimal PHSMs was sufficient to avoid strict lockdowns. At lesser coverage (≤ 60%) rapid case escalation risked overwhelming of the health sector and would prompt a need to reimpose strict restrictions, with substantive economic impacts in order to achieve the goals of the National Plan. Maintaining low case numbers was the most beneficial strategy for health and the economy, and at higher coverage levels (≥ 80%) further easing of restrictions was deemed possible. Interpretation These results reinforced recommendations from other modelling groups that some level of PHSMs should be continued to minimise the burden of the Delta variant following achievement of high population vaccine coverage. They directly informed easing of COVID-19 restrictions in Australia. Funding This study was supported by the Australian Government Department of Health and Ageing, and the National Health and Medical Research Council9s Centre of Research Excellence scheme (GNT1170960).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.15.22282869v2" target="_blank">Estimating measures to reduce the transmission of SARS-CoV-2 in Australia to guide a ‘National Plan’ to reopening</a>
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<li><strong>Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sublineages in the face of maturing antibody breadth at the population level</strong> -
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The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and related sub-lineages. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants at two levels: (i) we tracked over 420,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibody response in individuals using blood from strigently curated vaccine and convalescent cohorts. In pooled IgG samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases we observed increased antibody breadth to variants that were yet to be in circulation. Determination of viral neutralization at the cohort level supported equivalent coverage across prior and emerging variants with emerging isolates BQ.1.1, XBB.1, BR.2.1 and XBF the most evasive. Further, these emerging variants were resistant to Evusheld, whilst neutralization resistance to Sotrovimab was restricted to BQ.1.1 and XBF. We conclude at this current point in time that dominant variants can evade antibodies at levels equivalent to their most evasive lineage counterparts but sustain an entry phenotype that continues to promote an additional outgrowth advantage. In Australia, BR2.1 and XBF share this phenotype and are dominating across NSW and Victoria.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.12.06.22283000v3" target="_blank">Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sublineages in the face of maturing antibody breadth at the population level</a>
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<li><strong>SARS-CoV-2 Envelope protein triggers depression and dysosmia via TLR2 mediated neuroinflammation</strong> -
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Background: Depression and dysosmia have been regarded as the main neurological symptoms in COVID-19 patients, the mechanism of which remains unclear. Current studies have demonstrated that SARS-CoV-2 envelope protein served as a pro-inflammatory factor as sensed by Toll like receptor 2 (TLR2), suggesting the viral infection independent pathological feature of E protein. In this study, we aim to determine the role of E protein in depression, dysosmia and associated neuroinflammation in central nervous system (CNS). Methods: Depression and olfactory function were observed in both female and male mice as receiving intracisternal injection of envelope protein. Immunohistochemistry was applied in conjunction with RT-PCR to assess the glial activation, blood-brain barrier status and mediators synthesis in cortex, hippocampus and olfactory bulb. TLR2 was pharmacologically blocked to determine its role in E protein related depression and dysosmia. Results: Intracisternal injection of envelope protein evoked depression and dysosmia in both female and male mice. Immunohistochemistry suggested that envelope protein upregulated IBA1 and GFAP in cortex, hippocampus and olfactory bulb, while ZO-1 was downregulated. Moreover, IL-beta, TNF-alpha, IL-6, CCL2, MMP2 and CSF1 were upregulated in both cortex and hippocampus, whereas IL-beta, IL-6 and CCL2 were upregulated in olfactory bulb. Furtherly, inhibiting microglia, but not astrocyte, alleviated depression and dysosmia induced by envelope protein. Finally, RT-PCR and immunohistochemistry suggested that TLR2 was upregulated in cortex, hippocampus and olfactory bulb, the blocking of which mitigated depression and dysosmia induced by envelope protein. Conclusions: Our study demonstrates that envelope protein could directly induce depression and dysosmia together with obvious neuroinflammation in CNS. TLR2 mediated depression and dysosmia induced by envelope protein, which could serve as a promising therapeutic target for neurological manifestation in COVID-19 patients.
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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/10.1101/2023.01.15.524078v1" target="_blank">SARS-CoV-2 Envelope protein triggers depression and dysosmia via TLR2 mediated neuroinflammation</a>
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</div></li>
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<li><strong>T492I mutation alters SARS-CoV-2 properties via modulating viral non-structural proteins</strong> -
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The historically dominant SARS-CoV-2 Delta variants and the currently dominant Omicron variants carry a T492I substitution within the non-structural protein 4 (NSP4). Based on a combination of in silico analyses, we predicted that the T492I mutation increases the transmissibility and adaptability of the virus. We confirmed this hypothesis by performing competition experiments in hamsters and in human airway tissue culture models. Furthermore, we show that the T492I mutation also increases the replication capacity and infectiveness of the virus, and improves its ability to evade antibody neutralization induced by previous variants. Mechanistically, the T492I mutation increases cleavage efficiency of the viral main protease NSP5 by enhancing enzyme-substrate binding, resulting in increased production of nearly all non-structural proteins processed by NSP5. Importantly, T492I mutation suppresses the viral RNA associated chemokines in monocytic macrophages, which may contribute to the attenuated pathogenicity of Omicron variants. Our results highlight the importance of the NSP4 mutation in the evolutionary dynamics of SARS-CoV-2 and identify a novel target for the development of broad-spectrum antiviral agents.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.15.524090v1" target="_blank">T492I mutation alters SARS-CoV-2 properties via modulating viral non-structural proteins</a>
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<li><strong>Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome (LTCS) patients</strong> -
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Deep metabolomic, proteomic and immunologic phenotyping of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Within here, several studies described the role of metabolites, lipoproteins and inflammation markers during infection and in recovered patients. In fact, after SARS-CoV-2 viral infection almost 20-30% of patients experience persistent symptoms even after 12 weeks of recovery which has been defined as long-term COVID-19 syndrome (LTCS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these small biomolecules such as metabolites, lipoprotein, cytokines and chemokines altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters in an integrated fashion could predict the disease course may help to stratify LTCS patients from acute COVID-19 or recovered specimens and would help to elucidate a potential mechanistic role of these biomolecules during the disease course. Here, we report an integrated analysis of blood serum and plasma by in vitro diagnostics research NMR spectroscopy and flow cytometry-based cytokine quantification in a total of 125 individuals (healthy controls (HC; n=73), recovered (n=12), acute (n=7) and LTCS (n=33)). We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls or acute COVID-19 patients. Further correlational analysis of cytokines and metabolites indicated that creatine, glutamine, and high-density lipoprotein (HDL) phospholipids were distributed differentially amongst patients or individuals. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared to HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their creatinine, phenylalanine, succinate, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except IL-18 chemokine, which tended to be higher in LTCS patients and correlated positively with several amino acids (creatine, histidine, leucine, and valine), metabolites (lactate and 3-HB) and lipoproteins. The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict the ongoing severity of LTCS patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.13.523998v1" target="_blank">Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome (LTCS) patients</a>
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<li><strong>Redistribution and activation of CD16brightCD56dim NK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination</strong> -
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With the alarming surge in COVID-19 cases globally, vaccination must be prioritised to achieve herd immunity. Immune dysfunction is detected in the majority of patients with COVID-19; however, it remains unclear whether the immune responses elicited by COVID-19 vaccination function against the Omicron subvariant BA.2. Of the 508 Omicron BA.2-infected patients enrolled, 102 were unvaccinated controls and 406 were vaccinated. Despite the presence of clinical symptoms in both groups, vaccination led to a significant decline in nausea or vomiting, abdominal pain, headache, pulmonary infection, overall clinical symptoms, and a moderate rise in body temperature. Omicron BA.2-infected individuals were also characterised by a mild increase in both serum pro- and anti-inflammatory cytokine levels after vaccination. There were no significant differences or trend changes between T and B lymphocyte subsets; however, a significant expansion of NK lymphocytes in COVID-19-vaccinated patients was observed. Moreover, the most effective CD16brightCD56dim subsets of NK cells showed increased functional capacities, as evidenced by a significantly greater IFN-{gamma} secretion and stronger cytotoxic potential in Omicron BA.2-infected patients after vaccination. Collectively, these results suggest that COVID-19 vaccination interventions promote the redistribution and activation of CD16brightCD56dim NK cell subsets against viral infections, and could facilitate the clinical management of Omicron BA.2-infected patients.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.13.524025v1" target="_blank">Redistribution and activation of CD16brightCD56dim NK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination</a>
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<li><strong>The emergence of goblet inflammatory or ITGB6hi nasal progenitor cells determines age-associated SARS-CoV-2 pathogenesis</strong> -
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Children infected with SARS-CoV-2 rarely progress to respiratory failure, but the risk of mortality in infected people over 85 years of age remains high, despite vaccination and improving treatment options. Here, we take a comprehensive, multidisciplinary approach to investigate differences in the cellular landscape and function of paediatric (<11y), adult (30-50y) and elderly (>70y) nasal epithelial cells experimentally infected with SARS-CoV-2. Our data reveal that nasal epithelial cell subtypes show different tropism to SARS-CoV-2, correlating with age, ACE2 and TMPRSS2 expression. Ciliated cells are a viral replication centre across all age groups, but a distinct goblet inflammatory subtype emerges in infected paediatric cultures, identifiable by high expression of interferon stimulated genes and truncated viral genomes. In contrast, infected elderly cultures show a proportional increase in ITGB6hi progenitors, which facilitate viral spread and are associated with dysfunctional epithelial repair pathways. A video explaining this work can be found here - https://youtu.be/uExP4bx6D_A .
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.16.524211v1" target="_blank">The emergence of goblet inflammatory or ITGB6hi nasal progenitor cells determines age-associated SARS-CoV-2 pathogenesis</a>
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<li><strong>Enhanced transmissibility, infectivity and immune resistance of the SARS-CoV-2 Omicron XBB.1.5 variant</strong> -
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In 2022, we have elucidated the characteristics of a variety of newly emerging SARS-CoV-2 Omicron subvariants. At the end of 2022, the XBB.1.5 variant, an descendant of XBB.1 that acquired the S:F486P substitution, emerged and is rapidly spreading in the USA and is the latest variant of concern. Although the features of XBB.1.5 was already reported by another group as a preprint, we think multiple and independent evaluations important, and these reports are crucial for sustained global health. In this study, our epidemic dynamics analysis revealed that the relative effective reproduction number (Re) of XBB.1.5 is more than 1.2-fold greater than that of the parental XBB.1, and XBB.1.5 is outcompeting BQ.1.1, the predominant lineage in the USA as of December 2022. Our data suggest that XBB.1.5 will rapidly spread worldwide in the near future. Yeast surface display assay and pseudovirus assay respectively showed that the ACE2 binding affinity and infectivity of XBB.1.5 is 4.3-fold and 3.3-fold higher than those of XBB.1, respectively. Moreover, neutralization assay revealed that XBB.1.5 is robustly resistant to BA.2 breakthrough infection sera (41-fold versus B.1.1, 20-fold versus BA.2) and BA.5 breakthrough infection sera (32-fold versus B.1.1, 9.5-fold versus BA.5), respectively. Because the immune resistance of XBB.1.5 is comparable to that of XBB.1, our results suggest that XBB.1.5 is the most successful XBB lineage as of January 2023 by acquiring the S:F486P substitution to augment ACE2 binding affinity without losing remarkable immune resistance, which leads to greater transmissibility.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.16.524178v1" target="_blank">Enhanced transmissibility, infectivity and immune resistance of the SARS-CoV-2 Omicron XBB.1.5 variant</a>
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<li><strong>Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants</strong> -
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Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots. Their impact on viral infection, transmission, and efficacy of vaccines and therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.1.1. and XBB.1 variants bind ACE2 with high affinity and promote membrane fusion more efficiently than earlier Omicron variants. Structures of the BQ.1.1 and XBB.1 RBDs bound to human ACE2 and S309 Fab (sotrovimab parent) explain the altered ACE2 recognition and preserved antibody binding through conformational selection. We show that sotrovimab binds avidly to all Omicron variants, promotes Fc-dependent effector functions and protects mice challenged with BQ.1.1, the variant displaying the greatest loss of neutralization. Moreover, in several donors vaccine-elicited plasma antibodies cross-react with and trigger effector functions against Omicron variants despite reduced neutralizing activity. Cross-reactive RBD-directed human memory B cells remained dominant even after two exposures to Omicron spikes, underscoring persistent immune imprinting. Our findings suggest that this previously overlooked class of cross-reactive antibodies, exemplified by S309, may contribute to protection against disease caused by emerging variants through elicitation of effector functions.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.17.523798v1" target="_blank">Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants</a>
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<li><strong>A qualitative study of positive psychological experiences and helpful coping behaviours among young people and older adults in the UK during the COVID-19 pandemic</strong> -
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While much research has focused on challenges that younger and older people have faced during the COVID-19 pandemic, little attention has been given to the capacity for resilience among these groups. We therefore explored positive psychological experiences and coping behaviours that protected mental health and well-being. Participants were 40 young people (aged 13-24) and 28 older adults (aged 70+) living in the UK during the COVID-19 pandemic. Interviews were held between May 2020 and January 2021. We generated six themes using qualitative thematic analysis, including: engagement in self-fulfilling activities, increased sense of social cohesion, personal growth, use of problem-focused strategies to manage pandemic-related stressors, giving and receiving social and community support, and utilising strategies to regulate thoughts and emotions. While all six themes were relevant both to younger and older adults, there were nuances in how each was experienced and enacted. For example, many older adults adjusted their routines given worries about virus vulnerability, while some young people experienced greater personal growth amidst increased awareness of mental health as they navigated the various lockdown restrictions.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/3wbmp/" target="_blank">A qualitative study of positive psychological experiences and helpful coping behaviours among young people and older adults in the UK during the COVID-19 pandemic</a>
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<li><strong>Structural insights into ligand-recognition, activation, and signaling-bias at the complement C5a receptor, C5aR1</strong> -
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Activation of the complement cascade is a critical part of our innate immune response against invading pathogens, and it operates in a concerted fashion with the antibodies and phagocytic cells towards the clearance of pathogens. The complement peptide C5a, generated during the activation of complement cascade, is a potent inflammatory molecule, and increased levels of C5a are implicated in multiple inflammatory disorders including the advanced stages of COVID-19 pathophysiology. The proximal step in C5a-mediated cellular and physiological responses is its interaction with two different seven transmembrane receptors (7TMRs) known as C5aR1 and C5aR2. Despite a large body of functional data on C5a-C5aR1 interaction, direct visualization of their interaction at high-resolution is still lacking, and it represents a significant knowledge gap in our current understanding of complement receptor activation and signaling. Here, we present cryo-EM structures of C5aR1 activated by its natural agonist C5a, and a G-protein-biased synthetic peptide ligand C5apep, in complex with heterotrimeric G-proteins. The C5a-C5aR1 structure reveals the ligand binding interface involving the N-terminus and extracellular loops of the receptor, and we observe that C5a exhibits a significant conformational change upon its interaction with the receptor compared to the basal conformation. On the other hand, the structural details of C5apep-C5aR1 complex provide a molecular basis to rationalize the ability of peptides, designed based on the carboxyl-terminus sequence of C5a, to act as potent agonists of the receptor, and also the mechanism underlying their biased agonism. In addition, these structural snapshots also reveal activation-associated conformational changes in C5aR1 including outward movement of TM6 and a dramatic rotation of helix 8, and the interaction interface for G-protein-coupling. In summary, this study provides previously lacking molecular basis for the complement C5a recognition and activation of C5aR1, and it should facilitate structure-based discovery of novel lead molecules to target C5aR1 in inflammatory disorders.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.01.14.524051v1" target="_blank">Structural insights into ligand-recognition, activation, and signaling-bias at the complement C5a receptor, C5aR1</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>Digital Tools to Expand COVID-19 Testing in Exposed Individuals in Cameroon</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: Digital based contact tracing<br/><b>Sponsors</b>: Elizabeth Glaser Pediatric AIDS Foundation; Find<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>Postural Changes and Severe COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Behavioral: Postural interventions based on pulmonary imaging<br/><b>Sponsor</b>: Wuhan Union Hospital, China<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>Efficacy and Safety of Jaktinib in Patients With COVID-19 Pneumonia.</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: Jaktinib; Drug: Placebo<br/><b>Sponsor</b>: First Affiliated Hospital of Zhejiang 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>Awaken Prone Positioning Ventinlation in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Awaken prone positioning ventilation<br/><b>Sponsor</b>: Southeast University, China<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>Effect of a Traditional Chinese Medicine Formulation on COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Traditional Chinese Medicine Formulation; Other: Placebo Treatment<br/><b>Sponsor</b>: First Affiliated Hospital Xi’an Jiaotong 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 of SHEN26 Capsule in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: SHEN26 dose 1; Drug: SHEN26 dose 2; Drug: SHEN26 placebo<br/><b>Sponsor</b>: Shenzhen Kexing Pharmaceutical 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 on the Safety and Efficacy of Meplazumab for Injection in Severe Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab for injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio 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>Bright Light Therapy for Post-COVID-19 Fatigue</strong> - <b>Condition</b>: Post COVID-19 Condition<br/><b>Interventions</b>: Device: Bright light therapy; Device: Dim red light therapy<br/><b>Sponsor</b>: Chinese University of Hong Kong<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 on the Safety and Efficacy of Meplazumab for Injection in Adults With Mild and Moderate COVID-19 Infections</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Meplazumab foe injection; Other: Normal saline<br/><b>Sponsor</b>: Jiangsu Pacific Meinuoke Bio 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>Oropharyngeal Immunoprophylaxis With High Polyphenolic Olive Oil as Clinical Spectrum Mitigating Factor in COVID-19.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Dietary Supplement: High polyphenolic olive oil. (Early harvest olive oil).<br/><b>Sponsor</b>: Hospital General Nuestra Señora del Prado<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Randomized, Phase I Study of DNA Vaccine OC-007 as a Booster Dose of COVID-19 Vaccine</strong> - <b>Conditions</b>: COVID-19 Respiratory Infection; COVID-19 Vaccine Adverse Reaction<br/><b>Interventions</b>: Biological: DNA vaccine OC-007; Other: Placebo<br/><b>Sponsor</b>: Matti Sällberg<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>Evaluate the Efficacy and Safety of FB2001 for Inhalation in Patients With Mild to Moderate COVID-19</strong> - <b>Condition</b>: Mild to Moderate COVID-19<br/><b>Interventions</b>: Drug: FB2001; Drug: FB2001 placebo<br/><b>Sponsor</b>: Frontier Biotechnologies Inc.<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>UC-MSCs in the Treatment of Severe and Critical COVID-19 Patients</strong> - <b>Conditions</b>: Mesenchymal Stem Cell; COVID-19 Pneumonia<br/><b>Interventions</b>: Biological: umbilical cord mesenchymal stem cells; Drug: paxlovid<br/><b>Sponsor</b>: Shanghai East 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>An Investigator Initiated, Randomized, Double-blinded, Placebo-controlled Clinical Trial to Evaluate the Safety, Immunogenicity and Efficacy of the Recombinant Two-component COVID-19 Vaccine (CHO Cell) in Adults Aged 18 Years and Older</strong> - <b>Condition</b>: Prevention of COVID-19 Caused by SARS-CoV-2<br/><b>Intervention</b>: Biological: randomized, double-blinded, placebo-controlled<br/><b>Sponsor</b>: Yu Qin<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>Evaluate the Efficacy and Safety of Azvudine in Preventing SARS-Cov-2 Infection in Ousehold in China</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Azvudine; Drug: Placebo<br/><b>Sponsors</b>: Shanghai Henlius Biotech; Huashan Hospital; Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.; HeNan Sincere Biotech Co., Ltd<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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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Potential of plant extracts in targeting SARS-CoV-2 main protease: an <em>in vitro</em> and <em>in silico</em> study</strong> - The deaths caused by the covid-19 pandemic have recently decreased due to a worldwide effort in vaccination campaigns. However, even vaccinated people can develop a severe form of the disease that requires ICU admission. As a result, the search for antiviral drugs to treat these severe cases has become a necessity. In this context, natural products are an interesting alternative to synthetic medicines used in drug repositioning, as they have been consumed for a long time through traditional…</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>Functionalized Fullerene for Inhibition of SARS-CoV-2 Variants</strong> - As virus outbreaks continue to pose a challenge, a nonspecific viral inhibitor can provide significant benefits, especially against respiratory viruses. Polyglycerol sulfates recently emerge as promising agents that mediate interactions between cells and viruses through electrostatics, leading to virus inhibition. Similarly, hydrophobic C(60) fullerene can prevent virus infection via interactions with hydrophobic cavities of surface proteins. Here, two strategies are combined to inhibit…</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>Detailed Insights into the Inhibitory Mechanism of New Ebselen Derivatives against Main Protease (M<sup>pro</sup>) of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)</strong> - SARS-CoV-2 main protease (M<sup>(pro)/3CL</sup>(pro)) is a crucial target for therapeutics, which is responsible for viral polyprotein cleavage and plays a vital role in virus replication and survival. Recent studies suggest that 2-phenylbenzisoselenazol-3(2H)-one (ebselen) is a potent covalent inhibitor of M^(pro), which affects its enzymatic activity and virus survival. Herein, we synthesized various ebselen derivatives to understand the mechanism of M^(pro) inhibition by ebselen. Using ebselen…</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 Z-RNA activates the ZBP1-RIPK3 pathway to promote virus-induced inflammatory responses</strong> - SARS-CoV-2 infection can trigger strong inflammatory responses and cause severe lung damage in COVID-19 patients with critical illness. However, the molecular mechanisms by which the infection induces excessive inflammatory responses are not fully understood. Here, we report that SARS-CoV-2 infection results in the formation of viral Z-RNA in the cytoplasm of infected cells and thereby activates the ZBP1-RIPK3 pathway. Pharmacological inhibition of RIPK3 by GSK872 or genetic deletion of MLKL…</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>D614G SARS-CoV-2 Pseudovirus Infectivity and Binding of Spike Protein to the ACE2 Receptor Inversely Correlates with Serum SARS-CoV-2-Specific IgG Levels</strong> - Understanding the functional characteristics of antibodies produced against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will assist in the determination of disease outcomes for this virus. In this study, the ability of antibodies to inhibit viral entry into the host cell through the interaction of the receptor binding domain of the viral spike protein and the angiotensin-converting enzyme 2 receptor on the human cell surface was investigated. The SARS-CoV-2 IgG levels in 20…</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>Discovery of Natural Bisbenzylisoquinoline Analogs from the Library of Thai Traditional Plants as SARS-CoV-2 3CL<sup>Pro</sup> Inhibitors: <em>In Silico</em> Molecular Docking, Molecular Dynamics, and <em>In Vitro</em> Enzymatic Activity</strong> - The emergence of SARS-CoV-2 in December 2019 has become a global issue due to the continuous upsurge in patients and the lack of drug efficacy for treatment. SARS-CoV-2 3CL^(Pro) is one of the most intriguing biomolecular targets among scientists worldwide for developing antiviral drugs due to its relevance in viral replication and transcription. Herein, we utilized computer-assisted drug screening to investigate 326 natural products from Thai traditional plants using structure-based virtual…</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>Discovery of All-d-Peptide Inhibitors of SARS-CoV-2 3C-like Protease</strong> - During the replication process of SARS-CoV-2, the main protease of the virus [3-chymotrypsin-like protease (3CL^(pro))] plays a pivotal role and is essential for the life cycle of the pathogen. Numerous studies have been conducted so far, which have confirmed 3CL^(pro) as an attractive drug target to combat COVID-19. We describe a novel and efficient next-generation sequencing (NGS) supported phage display selection strategy for the identification of a set of SARS-CoV-2 3CL^(pro) targeting…</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>High Throughput Screening for Drugs that Inhibit 3C-Like Protease in SARS-CoV-2</strong> - The SARS coronavirus 2 (SARS-CoV-2) pandemic remains a major problem in many parts of the world and infection rates remain at extremely high levels. This high prevalence drives the continued emergence of new variants, and possibly ones that are more vaccine-resistant and that can drive infections even in highly vaccinated populations. The high rate of variant evolution makes clear the need for new therapeutics that can be clinically applied to minimize or eliminate the effects of COVID-19. With…</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>Relationship between behavioral inhibition/activation system and Internet addiction among Chinese college students: The mediating effects of intolerance of uncertainty and self-control and gender differences</strong> - CONCLUSIONS: These findings extend our understanding of how BIS/BAS influence Internet addiction among college students and suggest that not only should training approaches based on intolerance of uncertainty and self-control be fully considered, but different intervention programs should be focused on gender sensitivity to maximize the intervention effect.</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>miR-615 facilitates porcine epidemic diarrhea virus replication by targeting <em>IRAK1</em> to inhibit type III interferon expression</strong> - Porcine epidemic diarrhea virus (PEDV) in the Coronavirus family is a highly contagious enteric pathogen in the swine industry, which has evolved mechanisms to evade host innate immune responses. The PEDV-mediated inhibition of interferons (IFNs) has been linked to the nuclear factor-kappa B (NF-κB) pathway. MicroRNAs (miRNAs) are involved in virus-host interactions and IFN-I regulation. However, the mechanism by which the PEDV regulates IFN during PEDV infection has not yet been investigated in…</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>Eugenol Alleviates TGEV-Induced Intestinal Injury via Suppressing ROS/NLRP3/GSDMD-Dependent Pyroptosis</strong> - Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Pyroptosis is involved in the pathogenesis of coronavirus, but its role in TGEV-induced intestinal injury has yet to be fully elucidated. Eugenol, an essential plant oil, plays a vital role in antiviral innate immune responses. We demonstrate the preventive effect of eugenol on TGEV infection. Eugenol alleviates TGEV-induced…</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>Relationship between toxicity and oxidative stress of the nanoencapsulated colchicine in a model of <em>Drosophila melanogaster</em></strong> - Drug repurposing allows searching for new biological targets, especially against emerging diseases such as Covid-19. Drug colchicine (COL) presents recognized anti-inflammatory action, while the nanotechnology purpose therapies with low doses, efficacy, and decrease the drug’s side-effects. This study aims to evaluate the effects of COL and colchicine nanocapsules (NCCOL) on survival, LC50, activity locomotor, and oxidative stress parameters, elucidating the toxicity profile in acute and chronic…</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>Flavonoids from the roots and rhizomes of Sophoratonkinensis and their in vitro anti-SARS-CoV-2 activity</strong> - Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and safety in healthy adults of full dose versus half doses of COVID-19 vaccine (ChAdOx1-S or BNT162b2) or full-dose CoronaVac administered as a booster dose after priming with CoronaVac: a randomised, observer-masked, controlled trial in Indonesia</strong> - BACKGROUND: Inactivated COVID-19 vaccines effectively prevent death, but their effectiveness for preventing infection or severe illness is known to decrease within 3-6 months following the second priming dose. Here we aimed to evaluate the immunogenicity and safety of three potential booster vaccines administered as a full-dose homologous booster or full-dose or half-dose heterologous boosters among individuals primed with CoronaVac.</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>Preclinical development of kinetin as a safe error-prone SARS-CoV-2 antiviral able to attenuate virus-induced inflammation</strong> - Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell…</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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