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184 lines
46 KiB
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<title>28 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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<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>Rapid resistance profiling of SARS-CoV-2 protease inhibitors</strong> -
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Resistance to nirmatrelvir (Paxlovid) has been shown by multiple groups and may already exist in clinical SARS-CoV-2 isolates. Here a panel of SARS-CoV-2 main protease (Mpro) variants and a robust cell-based assay are used to compare the resistance profiles of nirmatrelvir, ensitrelvir, and FB2001. The results reveal distinct resistance mechanisms (fingerprints) and indicate that these next-generation drugs have the potential to be effective against nirmatrelvir-resistant variants and vice versa.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.25.530000v1" target="_blank">Rapid resistance profiling of SARS-CoV-2 protease inhibitors</a>
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<li><strong>Binding of SARS-CoV-2 non-structured protein 1 to 40S ribosome inhibits mRNA translation</strong> -
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Experiments have shown that non-structural protein 1 (NSP1) of SARS-CoV-2 is a factor that restricts cellular gene expression and prevents mRNA translation in the ribosome 40S subunit. However, the molecular mechanism of this phenomenon remains unclear. To clarify this issue, all-atom steered molecular dynamics and coarse-grained alchemical simulations were used to compare the binding affinity of mRNA to 40S ribosome in the absence and presence of NSP1. We found that NSP1 binding to the 40S ribosome dramatically increases the binding affinity of mRNA, which, in agreement with experiment, suggests that NSP1 can stall mRNA translation. The mRNA translation has been found to be driven by electrostatic mRNA-40S ribosome interactions. Water molecules have been demonstrated to play an important role in stabilizing the mRNA-40S ribosome complex. The NSP1 residues that are critical in triggering a translation arrest have been identified.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.24.529933v1" target="_blank">Binding of SARS-CoV-2 non-structured protein 1 to 40S ribosome inhibits mRNA translation</a>
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</div></li>
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<li><strong>Cutaneous jet-injection of naked mRNA vaccine induces robust immune responses without systemic vaccine spillage</strong> -
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Locally injected lipid nanoparticle (LNP)-based mRNA vaccines migrate systemically, which could raise safety concerns. From a mechanistic viewpoint, whether local or systemic antigen expression contributes to the vaccine effects remains unclear. Herein, we localized the antigen protein expression using naked mRNA and drastically improved the delivery efficiency in the skin by jet injection. Consequently, jet-injected naked mRNA outperformed a widely-used LNP in humoral immunity induction at the highest tolerable mRNA doses of each formulation in mice. A mechanistic investigation suggests that antigen-presenting cells taking up antigens at the jet-injection site of naked mRNA migrate to draining lymph nodes, enabling robust immunization without systemic mRNA distribution. Ultimately, jet injection of SARS-CoV-2 spike mRNA provided efficient antibody responses, neutralizing potential and cellular immunity in rodents and non-human primates with no reactogenicity. Conclusively, naked mRNA jet injection is a robust, tolerable, and simple vaccine candidate.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.27.530188v1" target="_blank">Cutaneous jet-injection of naked mRNA vaccine induces robust immune responses without systemic vaccine spillage</a>
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<li><strong>Cell Surface Nucleocapsid Protein Expression: A Betacoronavirus Immunomodulatory Strategy</strong> -
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We recently reported that SARS-CoV-2 Nucleocapsid (N) protein is abundantly expressed on the surface of both infected and neighboring uninfected cells, where it enables activation of Fc receptor-bearing immune cells with anti-N antibodies (Abs) and inhibits leukocyte chemotaxis by binding chemokines (CHKs). Here, we extend these findings to N from the seasonal human coronavirus (HCoV)-OC43, which is also robustly expressed on the surface of infected and non-infected cells by binding heparan-sulfate/heparin (HS/H). HCoV-OC43 N binds with high affinity to the same set of 11 human CHKs as SARS-CoV-2 N, but also to a non-overlapping set of 6 cytokines (CKs). As with SARS-CoV-2 N, HCoV-OC43 N inhibits CXCL12{beta}-mediated leukocyte migration in chemotaxis assays, as do all highly pathogenic and endemic HCoV N proteins. Together, our findings indicate that cell surface HCoV N plays important evolutionary conserved roles in manipulating host innate immunity and as a target for adaptive immunity.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.24.529952v1" target="_blank">Cell Surface Nucleocapsid Protein Expression: A Betacoronavirus Immunomodulatory Strategy</a>
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<li><strong>Genomic perspectives of SARS CoV-2 in liver disease patients with its clinical correlation: A single centre retrospective study</strong> -
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<div>
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Background: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2), is a causative agent of current global pandemic of Coronavirus disease-19 (COVID-19). Due to propagated outbreak and global vaccination drive an immense immunological selection pressure has been exerted on SARS CoV-2 leading to evolution of new variants. This study was performed to compare the mutational and clinical profile of liver disease patients infected with different variants of SARS CoV-2. Methodology: This was a single-centre, retrospective, cohort study in which clinicogenomic analysis of liver disease (LD) patients infected with SARS CoV-2 was performed. Complete demographic and clinical details were retrieved from Hospital Information System (HIS). QC-threshold passed FASTA files containing sequences from COVID-19 patients (n=174) were compared with a reference genome of SARS-CoV-2 isolate named Wuhan-Hu-1 (NCBI Reference Sequence: NC_045512.2) for mutational analysis. Results: Out of 232 finally analysed patients 137 (59.1%) were LD-CoV (+) and 95 (40.9%) were LD-CoV(-). LD patients with comorbidities were affected more with COVID-19 (p=0.002). On comparing the outcome in the terms of mortality, LD-CoV (+) had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher of odds of succumbing to COVID-19 (p=0.006). Multivariate regression analysis revealed, abdominal distention (p=0.05), severe COVID-19 pneumonia (p=0.046) and the change in serum bilirubin levels (p=0.005) as well as Alkaline phosphatase (ALP) levels (p=0.003) to have an association with adverse outcome in LD patients with COVID-19. In Delta (22%) and Omicron (48%) groups, Spike gene harboured maximum mutations. On comparing the mutations between LD-CoV(+/D) and LD-CoV(+/O) a total of nine genes had more mutations in LD-CoV(+/O) whereas three genes had more mutations in LD-CoV(+/D). Conclusion: We concluded that LD patients are more susceptible to COVID-19 as compared to a healthy adult with associated adverse clinical outcomes in terms of mortality and morbidity. Therefore this special group should be given priority while devising and introducing new vaccination and vaccination policies. The infection with different variants did not result in different outcome in our group of patients. Keywords: COVID-19, SARS CoV-2, Delta, Omicron, Liver disease
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.26.530067v1" target="_blank">Genomic perspectives of SARS CoV-2 in liver disease patients with its clinical correlation: A single centre retrospective study</a>
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<li><strong>A comparative analysis of state-of-the-art AI-based protein folding applied to SARS-CoV-2</strong> -
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This paper discusses the importance of identifying and understanding the Variants of Concern (VOC) of COVID-19, which are mutations of the SARS-CoV-2 virus that have the potential to increase transmission, severity of disease, or the ability to evade immune responses. Protein modeling can be used to understand the structure of SARS-CoV-2 and its components, such as the spike protein. This paper presents a comparative study between the current state-of-the-art software for protein folding by applying them to different variants of the spike protein of SARS-CoV-2 and showcasing the resulting TM-scores.
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🖺 Full Text HTML: <a href="https://osf.io/vrmxe/" target="_blank">A comparative analysis of state-of-the-art AI-based protein folding applied to SARS-CoV-2</a>
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<li><strong>A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling</strong> -
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Altered myeloid inflammation and lymphopenia are hallmarks of severe infections, including SARS-CoV-2. Here, we identified a gene program, defined by correlation with EN-RAGE (S100A12) gene expression, which was up-regulated in patient airway and blood myeloid cells. The EN-RAGE program was expressed in 7 cohorts and observed in patients with both COVID-19 and acute respiratory distress syndrome (ARDS) from other causes. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGE+ myeloid cells express features consistent with suppressor cell functionality, with low HLA-DR and high PD-L1 surface expression and higher expression of T cell-suppressive genes. Sustained EN-RAGE signature expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers, such as PD-1. IL-6 upregulated many of the severity-associated genes in the EN-RAGE gene program in vitro, along with potential mediators of T cell suppression, such as IL-10. Blockade of IL-6 signaling by tocilizumab in a placebo-controlled clinical trial led to rapid normalization of ENRAGE and T cell gene expression. This identifies IL-6 as a key driver of myeloid dysregulation associated with worse clinical outcomes in COVID-19 patients and provides insights into shared pathophysiological mechanisms in non-COVID-19 ARDS.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.07.22282049v2" target="_blank">A myeloid program associated with COVID-19 severity is decreased by therapeutic blockade of IL-6 signaling</a>
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<li><strong>Evaluation of primary allied healthcare in patients recovering from COVID-19: first results after six months follow-up in a Dutch nationwide prospective cohort study</strong> -
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Objectives: To report the recovery of patients receiving primary allied healthcare after a COVID-19 infection at a six-month follow-up, and to explore which patient characteristics are associated with the changes in outcomes between the baseline and six-month follow-up. Design: Prospective cohort study. Setting: Allied healthcare in Dutch primary care. Participants: 1,451 adult patients recovering from COVID-19 and receiving treatment from one or more primary care allied health professional(s) (i.e., dietitian, exercise therapist, occupational therapist, physical therapist and/or speech and language therapist). Results: For participation (USER-P range 0 to 100), estimated mean differences of at least 2.3 points were observed after six months. For HRQoL (EQ-VAS range 0 to 100), the mean increase was 12.31 at six months. Furthermore, significant improvements were found for fatigue (FSS range 1 to 7): the mean decrease was -0.7 at six months. For physical functioning (PROMIS-PF range 13.8 to 61.3), the mean increase was 5.9 at six months. Mean differences of -0.8 for anxiety (HADS range 0 to 21), and -1.5 for depression (HADS range 0 to 21), were found after six months. Having a worse baseline score, hospital admission and male sex were associated with greater improvement between the baseline and six-month follow-up, whereas age, BMI, comorbidities and smoking status were not associated with mean changes in any outcome measure. Conclusions: Patients recovering from COVID-19 who receive primary allied healthcare make progress in recovery, but still experience many limitations in their daily activities after six months. Our findings provide reference values to healthcare providers and healthcare policy-makers regarding what to expect from the recovery of patients who received health care from one or more primary care allied health professionals. Trial registration: Clinicaltrials.gov registry (NCT04735744).
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.10.03.22280639v3" target="_blank">Evaluation of primary allied healthcare in patients recovering from COVID-19: first results after six months follow-up in a Dutch nationwide prospective cohort study</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/10.1101/2023.01.17.523798v2" target="_blank">Therapeutic and vaccine-induced cross-reactive antibodies with effector function against emerging Omicron variants</a>
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<li><strong>COVID-19 amplified racial disparities in the U.S. criminal legal system</strong> -
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The criminal legal system in the United States drives an incarceration rate that is the highest on the planet, with disparities by class and race among its signature features [1-3]. During the first year of the COVID-19 pandemic, the number of incarcerated people in the U.S. decreased by at least 17%—the largest, fastest reduction in prison population in American history [4]. In this study, we ask how this reduction influenced the racial composition of U.S. prisons, and consider possible mechanisms for these dynamics. Using an original dataset curated from public sources on prison demographics across all 50 states and the District of Columbia, we show that incarcerated white people benefited disproportionately from the decrease in the U.S. prison population, and that the fraction of incarcerated Black and Latino people sharply increased. This pattern of increased racial disparity exists across prison systems in nearly every state and reverses a decades-long trend before 2020 and the onset of COVID-19, when the proportion of incarcerated white people was increasing amid declining numbers of incarcerated Black people [5]. Although a variety of factors underlie these trends, we find that racial inequities in average sentence length are a major contributor. Ultimately, this study reveals how disruptions caused by COVID-19 exacerbated racial inequalities in the criminal legal system, and highlights key forces that sustain mass incarceration.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2021.12.14.21267199v3" target="_blank">COVID-19 amplified racial disparities in the U.S. criminal legal system</a>
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<li><strong>Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modeling study</strong> -
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<b>Background</b> Serological surveys have been the gold standard to estimate the numbers of SARS-CoV-2 infections, epidemic dynamics, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2. <b>Aim</b> Our goal is to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon. <b>Methods</b> We performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed individuals, without any SARS-CoV-2 vaccines, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients). <b>Results</b> Of the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depends strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We find that a third of the included assays depart considerably from manufacturer specifications after 6 months. <b>Conclusions</b> Seroassay sensitivity decay depends on assay characteristics, and for some types of assays it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon, and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens, and quantify systematic biases in the existing serology literature.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.09.08.22279731v3" target="_blank">Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modeling study</a>
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<li><strong>Interrelations of resilience factors and their incremental impact for mental health: Insights from network modeling using a prospective study across seven timepoints</strong> -
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Resilience as an outcome can be viewed as trajectory of stable good mental health or the quick regain of mental health during or after stressor exposure. Resilience factors (RFs) are psychological resources that buffer the potential negative effects of stress on mental health. A problem of resilience research is the large number of conceptually overlapping RFs complicating their understanding as well as the planning and evaluation of resilience interventions. The current study sheds light on interrelations of RFs in the face of the COVID-19 pandemic as a use case for major disruptions. The prospective study assessed a population sample of 1,275 German-speaking people (Mage=50.06, 51.5% female) from February 2020 to March 2021 at six critical timepoints during the pandemic. We assessed coping, hardiness, control beliefs, optimism, self-efficacy, sense of coherence (SOC), sense of mastery, social support as well as dispositional resilience as psychological RFs in February 2020, and mental health (i.e., psychopathological symptoms, COVID-19-related rumination, stress-related growth) at all timepoints. Analyses used partial correlation network models and LASSO regressions. Pre-pandemic RFs were strongly interrelated with SOC being the most central node. During the pandemic, networks for all outcomes remained stable. Pre-pandemic SOC was the strongest partial correlate of psychopathological symptoms and COVID-19-related rumination, while stress-related growth showed unique associations with positive reframing and optimism. LASSO regressions supported SOC’s incremental validity beyond other RFs for psychopathological symptoms and COVID-19-related rumination, while SOC was unrelated to stress-related growth. Either longitudinally or cross-sectionally, the sum of RFs at most accounted for 39% of the variance in mental health. Our findings provide evidence for SOC playing an important role for mental health and suggest to further examine SOC’s incremental validity. Given the differential associations for negative and positive mental health outcomes, resilience research may benefit from using multidimensional outcomes.
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🖺 Full Text HTML: <a href="https://osf.io/evkw5/" target="_blank">Interrelations of resilience factors and their incremental impact for mental health: Insights from network modeling using a prospective study across seven timepoints</a>
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<li><strong>MDTOMO: Continuous conformational variability analysis in cryo electron subtomogram data using flexible fitting based on Molecular Dynamics simulations</strong> -
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Cryo electron tomography (cryo-ET) allows observing macromolecular complexes in their native environment. The common routine of subtomogram averaging (STA) allows obtaining the three-dimensional (3D) structure of abundant macromolecular complexes, and can be coupled with discrete classification to reveal conformational heterogeneity of the sample. However, the number of complexes extracted from cryo-ET data is usually small, which restricts the discrete-classification results to a small number of enough populated states and, thus, results in a largely incomplete conformational landscape. Alternative approaches are currently being investigated to explore the continuity of the conformational landscapes that in situ cryo-ET studies could provide. In this article, we present MDTOMO, a method for analyzing continuous conformational variability in cryo-ET subtomograms based on Molecular Dynamics (MD) simulations. MDTOMO allows obtaining an atomic-scale model of conformational variability and the corresponding free-energy landscape, from a given set of cryo-ET subtomograms. The article presents the performance of MDTOMO on a synthetic ABC exporter dataset and an in situ SARS-CoV-2 spike dataset. MDTOMO allows analyzing dynamic properties of molecular complexes to understand their biological functions, which could also be useful for structure-based drug discovery.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.25.529934v1" target="_blank">MDTOMO: Continuous conformational variability analysis in cryo electron subtomogram data using flexible fitting based on Molecular Dynamics simulations</a>
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<li><strong>Prevalence of smell, taste and chemesthesis disorders among patients with the Omicron Variant of SARS-CoV-2 in China</strong> -
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Many studies have confirmed that chemosensory disorder (including smell, taste and chemesthesis) is one of the symptoms of COVID-19 infection. However, new data indicated that the changes of chemosensory sensation caused by COVID-19 may be different among different populations and COVID-19 variants. At present, there are few studies focusing on the influence of Omicron on qualitative changes and quantitative reductions of chemosensory in China. We conducted a cross‑sectional study on COVID-19 Omicron variant patients to investigate the prevalence of chemosensory disorders and their chemosensory function before and during infection by online questionnaire. A total of 1245 patients with COVID-19 completed the study. The prevalence of smell, taste and chemesthesis disorder was 69.2%, 67.7% and 31.4% respectively. Sex, age, smoking and COVID-19-related symptoms such as lack of appetite, dyspnea and fatigue may have association with chemosensory disorders during COVID-19. Self-ratings of chemosensory function revealed that patients experienced a decline in the function of smell, taste and chemesthesis generally. Further studies are needed to combine the data using objective assessment and investigate the factors affecting chemosensory in COVID-19 through longitudinal research.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.21.23286242v2" target="_blank">Prevalence of smell, taste and chemesthesis disorders among patients with the Omicron Variant of SARS-CoV-2 in China</a>
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<li><strong>A Snapshot of COVID-19 Incidence, Hospitalizations, and Mortality from Indirect Survey Data in China in January 2023</strong> -
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In this work we estimate the incidence of COVID-19 in China using online indirect surveys (which preserve the privacy of the participants). The indirect surveys deployed collect data on the incidence of COVID-19, asking the participants about the number of cases, deaths, vaccinated, and hospitalized that they know. The incidence of COVID-19 (cases, deaths, etc.) is then estimated using a modified Network Scale-up Method (NSUM). Survey responses (100, 200 and 1,000, respectively) were collected from Australia, the UK, and China in January 2023. The estimates in Australia and the UK are compared with official data, showing that they are in the confidence intervals or rather close. Cronbach9s alpha values also indicate good confidence in the estimates. The estimates obtained in China are, among others, that 91% of the population is vaccinated, almost 80% had been infected in the last month, and almost 3% in the last 24 hours.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.22.23286167v2" target="_blank">A Snapshot of COVID-19 Incidence, Hospitalizations, and Mortality from Indirect Survey Data in China in January 2023</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>Heterologous Booster Study of COVID-19 Protein Subunit Recombinant Vaccine in Children 12-17 Years of Age</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: SARS-CoV-2 subunit protein recombinant vaccine<br/><b>Sponsors</b>: PT Bio Farma; Faculty of Medicine Universitas Padjadjaran<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>Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: Aerobic exercise and strength training<br/><b>Sponsor</b>: Ukbe Sirayder<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluticasone; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<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>Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Blood sampling<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: N-Acetylcysteine; Drug: Placebo<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: miRNA analysis in plasma<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<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>Telerehabilitation in the Post-COVID-19 Patient (TRIALS)</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Istituto Auxologico Italiano<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>Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator<br/><b>Sponsor</b>: Hebei Medical University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Cognitive Rehabilitation for People With Cognitive Covid19</strong> - <b>Condition</b>: Long Covid19<br/><b>Intervention</b>: Behavioral: Cognitive rehabilitation<br/><b>Sponsors</b>: University College, London; Bangor University; St George’s University Hospitals NHS Foundation Trust; University of Brighton; University Hospital Southampton NHS Foundation Trust; Greater Manchester Mental Health NHS Foundation Trust<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>MGC Health COVID-19 & Flu A+B Home Multi Test Usability Study</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B<br/><b>Interventions</b>: Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test; Diagnostic Test: MGC Health COVID-19 & Flu A+B Home Multi Test (2 to 13 y/o)<br/><b>Sponsors</b>: Medical Group Care, LLC; CSSi Life Sciences<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>Washing COVID-19 Away With a Hypertonic Seawater Nasal Irrigation Solution</strong> - <b>Condition</b>: SARS-CoV2 Infection<br/><b>Intervention</b>: Other: Hypertonic seawater solution<br/><b>Sponsor</b>: Larissa University Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of HH-120 Nasal Spray in Close Contacts of Those Diagnosed With COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: HH-120 Nasal Spray<br/><b>Sponsor</b>: Beijing Ditan Hospital<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>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19<br/><b>Interventions</b>: Other: Individual Counseling; Other: Group Counseling; Other: Resources<br/><b>Sponsors</b>: New Mexico State University; National Institutes of Health (NIH)<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>To Evaluate the Safety, Efficacy,and Pharmacokinetics of Orally Administered Prolectin-M</strong> - <b>Conditions</b>: COVID-19; SARS CoV 2 Infection<br/><b>Intervention</b>: Drug: Prolectin-M<br/><b>Sponsor</b>: Bioxytran Inc.<br/><b>Not yet recruiting</b></p></li>
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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>An approach combining deep learning and molecule docking for drug discovery of cathepsin L</strong> - CONCLUSION: Our approach enables drug discovery from large-scale databases with little computational consumption, which will save the cost and time required for drug discovery.</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>Search of Novel Small Molecule Inhibitors for the Main Protease of SARS-CoV-2</strong> - The current outbreak of coronavirus disease 2019 (COVID-19) has prompted the necessity of efficient treatment strategies. The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Main protease (Mpro), also called 3-chymotrypsin-like protease (3CL protease), plays an essential role in cleaving virus polyproteins for the functional replication complex. Therefore, Mpro is a promising drug target for COVID-19 therapy. Through molecular modelling, docking…</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 Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19</strong> - COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell…</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 Validation of SARS-CoV-2-Inactivation and Viral Genome Stability in Saliva by a Guanidine Hydrochloride and Surfactant-Based Virus Lysis/Transport Buffer</strong> - To enhance biosafety and reliability in SARS-CoV-2 molecular diagnosis, virus lysis/transport buffers should inactivate the virus and preserve viral RNA under various conditions. Herein, we evaluated the SARS-CoV-2-inactivating activity of guanidine hydrochloride (GuHCl)- and surfactant (hexadecyltrimethylammonium chloride (Hexa-DTMC))-based buffer, Prep Buffer A, (Precision System Science Co., Ltd., Matsudo, Japan) and its efficacy in maintaining the stability of viral RNA at different…</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>Novel Tetrahydroisoquinoline-Based Heterocyclic Compounds Efficiently Inhibit SARS-CoV-2 Infection <em>In Vitro</em></strong> - The ongoing COVID-19 pandemic has caused over six million deaths and huge economic burdens worldwide. Antivirals against its causative agent, SARS-CoV-2, are in urgent demand. Previously, we reported that heterocylic compounds, i.e., chloroquine (CQ) and hydroxychloroquine (HCQ), are potent in inhibiting SARS-CoV-2 replication in vitro. In this study, we discussed the syntheses of two novel heterocylic compounds: tert-butyl…</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>Antiviral Activity of Micafungin and Its Derivatives against SARS-CoV-2 RNA Replication</strong> - Echinocandin antifungal drugs, including micafungin, anidulafungin, and caspofungin, have been recently reported to exhibit antiviral effects against various viruses such as flavivirus, alphavirus, and coronavirus. In this study, we focused on micafungin and its derivatives and analyzed their antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The micafungin derivatives Mi-2 and Mi-5 showed higher antiviral activity than micafungin, with 50% maximal…</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>Crude Extracts of <em>Talaromyces</em> Strains (Ascomycota) Affect Honey Bee (<em>Apis mellifera</em>) Resistance to Chronic Bee Paralysis Virus</strong> - Viruses contribute significantly to the global decline of honey bee populations. One way to limit the impact of such viruses is the introduction of natural antiviral compounds from fungi as a component of honey bee diets. Therefore, we examined the effect of crude organic extracts from seven strains of the fungal genus Talaromyces in honey bee diets under laboratory conditions. The strains were isolated from bee bread prepared by honey bees infected with chronic bee paralysis virus (CBPV). 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>How Different Pathologies Are Affected by IFIT Expression</strong> - The type-I interferon (IFN) system represents the first line of defense against viral pathogens. Recognition of the virus initiates complex signaling pathways that result in the transcriptional induction of IFNs, which are then secreted. Secreted IFNs stimulate nearby cells and result in the production of numerous proinflammatory cytokines and antiviral factors. Of particular note, IFN-induced tetratricopeptide repeat (IFIT) proteins have been thoroughly studied because of their antiviral…</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 D405N Mutation in the Spike Protein of SARS-CoV-2 Omicron BA.5 Inhibits Spike/Integrins Interaction and Viral Infection of Human Lung Microvascular Endothelial Cells</strong> - Severe COVID-19 is characterized by angiogenic features, such as intussusceptive angiogenesis, endothelialitis, and activation of procoagulant pathways. This pathological state can be ascribed to a direct SARS-CoV-2 infection of human lung ECs. Recently, we showed the capability of SARS-CoV-2 to infect ACE2-negative primary human lung microvascular endothelial cells (HL-mECs). This occurred through the interaction of an Arg-Gly-Asp (RGD) motif, endowed on the Spike protein at position 403-405,…</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>EPAC1 Pharmacological Inhibition with AM-001 Prevents SARS-CoV-2 and Influenza A Virus Replication in Cells</strong> - The exceptional impact of the COVID-19 pandemic has stimulated an intense search for antiviral molecules. Host-targeted antiviral molecules have the potential of presenting broad-spectrum antiviral activity and are also considered as less likely to select for resistant viruses. In this study, we investigated the antiviral activity exerted by AM-001, a specific pharmacological inhibitor of EPAC1, a host exchange protein directly activated by cyclic AMP (cAMP). The cAMP-sensitive protein, EPAC1…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Molecular Epidemiology of SARS-CoV-2: The Dominant Role of Arginine in Mutations and Infectivity</strong> - Background, Aims, Methods, Results, Conclusions: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global challenge due to its ability to mutate into variants that spread more rapidly than the wild-type virus. The molecular biology of this virus has been extensively studied and computational methods applied are an example paradigm for novel antiviral drug therapies. The rapid evolution of SARS-CoV-2 in the human population is driven, in part, by mutations in the receptor-binding…</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>Protein Arginylation Is Regulated during SARS-CoV-2 Infection</strong> - CONCLUSIONS: We demonstrate that ATE1 is increased during SARS-CoV-2 infection and its inhibition has potential therapeutic value.</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>Quinazolinone-Peptido-Nitrophenyl-Derivatives as Potential Inhibitors of SARS-CoV-2 Main Protease</strong> - The severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2-M^(pro)) plays an essential role in viral replication, transcription, maturation, and entry into host cells. Furthermore, its cleavage specificity for viruses, but not humans, makes it a promising drug target for the treatment of coronavirus disease 2019 (COVID-19). In this study, a fragment-based strategy including potential antiviral quinazolinone moiety and glutamine- or glutamate-derived peptidomimetic backbone 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>Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice</strong> - This paper presents a novel approach for improving the efficacy of COVID-19 vaccines against emergent SARS-CoV-2 variants. We have evaluated the immunogenicity of unadjuvanted wild-type (WU S1-RS09cg) and variant-specific (Delta S1-RS09cg and OM S1-RS09cg) S1 subunit protein vaccines delivered either as a monovalent or a trivalent antigen in BALB/c mice. Our results show that a trivalent approach induced a broader humoral response with more coverage against antigenically distinct variants,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs</strong> - SARS-CoV-2 has evolved as several variants. Immunization to boost the Ab response to Spike antigens is effective, but similar vaccines could not enhance Ab efficacy enough. Effective Ab responses against the human ACE2 (hACE2)-mediated infection of the emerging SARS-CoV-2 variants are needed. We identified closed linear epitopes of the SARS-CoV-2 Spike molecule that induced neutralizing Abs (nAbs) against both S1-RBD, responsible for attachment to hACE2, and S2-HR1/2, in convalescents and…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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