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<title>25 July, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>The use and acceptability of preprints in health and social care settings: a scoping review</strong> -
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<div>
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Background: Preprints are open and accessible scientific manuscript or report that is shared publicly, through a preprint server, before being submitted to a journal. The value and importance of preprints has grown since its contribution during the public health emergency of the COVID-19 pandemic. Funders and publishers are establishing their position on the use of preprints, in grant applications and publishing models. However, the evidence supporting the use and acceptability of preprints varies across funders, publishers, and researchers. The scoping review explored the current evidence on the use and acceptability of preprints in health and social care settings by publishers, funders, and the research community throughout the research lifecycle. Methods: A scoping review was undertaken with no study or language limits. The search strategy was limited to the last five years (2017-2022) to capture changes influenced by COVID-19 (e.g., accelerated use and role of preprints in research). The review included international literature, including grey literature, and two databases were searched: Scopus and Web of Science (24 August 2022). Results: 379 titles and abstracts and 193 full text articles were assessed for eligibility. Ninety-eight articles met eligibility criteria and were included for full extraction. For barriers and challenges, 26 statements were grouped under four main themes (e.g., volume/growth of publications, quality assurance/trustworthiness, risks associated to credibility, and validation). For benefits and value, 34 statements were grouped under six themes (e.g., openness/transparency, increased visibility/credibility, open review process, open research, democratic process/systems, increased productivity/opportunities). Conclusions: Preprints provide opportunities for rapid dissemination but there is a need for clear policies and guidance from journals, publishers, and funders. Cautionary measures are needed to maintain the quality and value of preprints, paying particular attention to how findings are translated to the public. More research is needed to address some of the uncertainties addressed in this review.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/nug4p/" target="_blank">The use and acceptability of preprints in health and social care settings: a scoping review</a>
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</div></li>
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<li><strong>Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2</strong> -
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<div>
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SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex consisting of nsp12, nsp7, and nsp8 as the key enzyme for viral genome replication and is a proven antiviral drug target. In this study, molecular interactions of nsp7 and nsp8 with nsp12 and the active site of nsp12 were coterminously targeted using in-silico screening of small molecule libraries to identify potential antivirals. Surface plasmon resonance (SPR) based assay using purified nsp7 and nsp8 proteins was developed, and the binding of identified molecules to targets was validated. The antiviral efficacy of identified small molecules was evaluated using cell-based assays, and potent antiviral effect with EC50 values of 0.56 uM, 0.73 uM, and 2.8 uM was demonstrated by fangchinoline, cepharanthine, and sennoside B, respectively. Further in vivo, investigation using hACE2 mice is being conducted. This is the first study that targets multiple sites in the RdRp complex of SARS-CoV-2 using a structure-based molecular repurposing approach and suggests potential therapeutic options for emerging variants of SARS-CoV-2.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.24.550324v1" target="_blank">Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2</a>
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</div></li>
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<li><strong>Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice</strong> -
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<div>
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Endothelial damage and vascular pathology have been recognized as major features of COVID-19 since the beginning of the pandemic. Two main theories regarding how Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) damages endothelial cells and causes vascular pathology have been proposed: direct viral infection of endothelial cells or indirect damage mediated by circulating inflammatory molecules and immune mechanisms. However, these proposed mechanisms remain largely untested in vivo. Here, we utilized a set of new mouse genetic tools1 developed in our lab to test both the necessity and sufficiency of endothelial human angiotensin-converting enzyme 2 (hACE2) in COVID19 pathogenesis. Our results demonstrate that endothelial ACE2 and direct infection of vascular endothelial cells does not contribute significantly to the diverse vascular pathology associated with COVID-19.
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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/10.1101/2023.07.24.550352v1" target="_blank">Endothelial SARS-CoV-2 infection is not the underlying cause of COVID19-associated vascular pathology in mice</a>
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</div></li>
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<li><strong>Biophysical principles predict fitness of SARS-CoV-2 variants</strong> -
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<div>
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SARS-CoV-2 is under constant selective pressure from antibodies while requiring efficient binding to host cells for successful infection. Here we focus specifically on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, a key determinant of viral entry into host cells. Through a comprehensive approach, comprising large-scale sequence analysis of SARS-CoV-2 variants and the formulation of a fitness function based on protein folding and binding thermodynamics, we unravel the relationship between the epidemiological fitness contribution of the RBD and its biophysical properties. We developed a biophysical model mapping the phenotype space, characterized by binding constants to cell receptors and antibodies, onto the fitness landscape for variants ranging from the ancestral Wuhan Hu-1 to the Omicron BA.1 . Using equilibrium statistical mechanics, we show how fitness can be expressed as a function of binding constants to cell receptors and antibodies and validate our findings through experimentally measured binding affinities and population data on frequencies of variants. This forms the basis for a comprehensive epistatic map, relating the genotype space to fitness. Our study thus delivers a tool for predicting the fitness of variants harboring previously unseen mutations, and sheds light on the impact of specific mutations on viral fitness. These insights offer not only greater understanding of viral evolution but also potentially aid in guiding public health decisions in the battle against COVID-19 and future pandemics.
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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/10.1101/2023.07.23.549087v1" target="_blank">Biophysical principles predict fitness of SARS-CoV-2 variants</a>
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</div></li>
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<li><strong>AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</strong> -
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<div>
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Metagenomic profiling algorithms commonly rely on genomic differences between lineages, strains or species to infer the relative abundances of sequences present in a sample. This observation plays an important role in the analysis of diverse microbial communities, where targeted sequencing of 16S and 18S rRNA, both well-known hypervariable genomic regions, have led to insights in microbial diversity and the discovery of novel organisms. However, the variable nature of discriminatory regions can also act as a double-edged sword, as the sought after variability can make it difficult to design primers for their amplification through PCR. Moreover, the most variable regions are not necessarily the most informative regions for the purpose of differentiation; one should focus on regions which maximize the number of lineages that can be distinguished. Here we present AmpliDiff, a computational tool that simultaneously finds such highly discriminatory genomic regions, as well as primers allowing for the amplification of these regions. We show that regions and primers found by AmpliDiff can be used to accurately estimate relative abundances of SARS-CoV-2 lineages, for example in wastewater sequencing data. We obtain mean absolute prediction errors that are comparable with using whole genome information to estimate relative abundances. Furthermore, our results show that AmpliDiff is robust against incomplete input data, and that primers designed by AmpliDiff continue to bind to genomes originating from months after the primers were selected. With AmpliDiff we provide an effective and efficient alternative to whole genome sequencing for estimating lineage abundances in viral metagenomes.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.22.550164v1" target="_blank">AmpliDiff: An Optimized Amplicon Sequencing Approach to Estimating Lineage Abundances in Viral Metagenomes</a>
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</div></li>
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<li><strong>Genomic epidemiology of European Aspergillus fumigatus causing COVID-19-associated pulmonary aspergillosis in Europe</strong> -
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<div>
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The opportunistic fungus Aspergillus fumigatus has been found to cause coinfections in patients with severe SARS-CoV-2 virus infection, leading to COVID-19-associated pulmonary aspergillosis (CAPA). The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole-resistance. Genomic epidemiology can help shed light on the genetics of A. fumigatus causing CAPA including the prevalence of alleles that are associated with azole-resistance. Here, a population genomic analysis of 21 CAPA isolates from four European countries is presented. The CAPA isolates were compared with A. fumigatus from a wider population of 167 non-CAPA clinical isolates and 73 environmental isolates. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically-encoded azole-resistant mechanisms. Phylogenetic analysis of the 21 CAPA isolates showed a lack of genetic distinction from the wider A. fumigatus population, with isolates distributed within two distinct clades (A and B), with the majority of the CAPA isolates in clade B (71.4%). The prevalence of phenotypic azole-resistance in CAPA was 14.3% (n=3/21); all three CAPA isolates contained a known resistance-associated cyp51A polymorphism. CAPA isolates are drawn from the wider A. fumigatus population rather than forming a unique genetic background showing that COVID-19 patients are susceptible to the entire A. fumigatus population. However, the relatively high prevalence of azole-resistance alleles that we document poses a threat to treatment success rates, warranting enhanced detection and surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes.
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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/10.1101/2023.07.21.550109v1" target="_blank">Genomic epidemiology of European Aspergillus fumigatus causing COVID-19-associated pulmonary aspergillosis in Europe</a>
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</div></li>
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<li><strong>Phylogeny and evolution of the SARS-CoV-2 spike gene from December 2022 to February 2023</strong> -
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<div>
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Background: By the end of 2022, new variants of SARS-CoV-2, such as BQ.1.1.10, BA.4.6.3, XBB, and CH.1.1, emerged with higher fitness than BA.5. Methods: The file (spikeprot0304), which contains spike protein sequences, isolates collected before March, 4, 2023, was downloaded from Global Initiative on Sharing All Influenza Data (GISAID). A total of 188 different spike protein sequences were chosen, of which their isolates were collected from December 2022 to February 2023. These sequences did not contain undetermined amino acid X, and each spike protein sequence had at least 100 identical isolate sequences in GISAID. Phylogenetic trees were reconstructed using IQ-TREE and MrBayes softwares. A median-join network was reconstructed using PopART software. Selection analyses were conducted using site model of PAML software. Results: The phylogenetic tree of the spike DNA sequences revealed that the majority of variants belonged to three major lineages: BA.2 (BA.1.1.529.2), BA.5 (BA.1.1.529.5), and XBB. The median network showed that these lineages had at least six major diversifying centers. The spike DNA sequences of these diversifying centers had the representative accession IDs (EPI_ISL_) of 16040256 (BN.1.2), 15970311 (BA.5), 16028739 (BA.5.11), 16028774 (BQ.1), 16027638 (BQ.1.1.23), and 16044705 (XBB.1.5). Selection analyses revealed 26 amino-acid sites under positive selection. These sites included L5, V83, W152, G181, N185, V213, H245, Y248, D253, S255, S256, G257, R346, R408, K444, V445, G446, N450, L452, N460, F486, Q613, Q675, T883, P1162, and V1264. Conclusion: The spike proteins of SARS-CoV-2 from December 2022 to February 2023 were characterized by a swarm of variants that were evolved from three major lineages: BA.2 (BA.1.1.529.2), BA.5 (BA.1.1.529.5), and XBB. These lineages had at least six diversifying centers. Selection analysis identified 26 amino acid sites were under positive selection. Continued surveillance and research are necessary to monitor the evolution and potential impact of these variants on public health.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.07.23.549423v1" target="_blank">Phylogeny and evolution of the SARS-CoV-2 spike gene from December 2022 to February 2023</a>
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</div></li>
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<li><strong>Factors influencing COVID-19 vaccination decision-making among African American and Hispanic pregnant and postpartum women in Deep South</strong> -
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Background COVID-19 vaccination is vital for ending the pandemic but concerns about its safety among pregnant and postpartum women, especially among African American (AA) and Hispanic women, persist. This study aims to explore factors that influence vaccination decision-making among AA and Hispanic pregnant and postpartum women through women’s experiences and maternal care providers’ (MCPs) observations. Methods From January and August 2022, we conducted semi-structured interviews with AA and Hispanic women and MCPs. Participants were recruited from obstetric and pediatric clinics in South Carolina, and all births took place after March 2020. Thematic analysis was employed for data analysis. Results The study involved 19 AA and 20 Hispanic women, along with 9 MCPs, and revealed both barriers and facilitators to COVID-19 vaccination. The factors that influence pregnant and postpartum women’s decision about COVID-19 vaccine uptake included: 1) awareness of health threats associated with COVID-19 vaccines, 2) vaccine availability and accessibility, 3) vaccine-related knowledge and exposure to misinformation, 4) concerns regarding pre-existing health conditions and potential side effects of COVID-19 vaccines, 5) emotional factors associated with vaccination decision-making processes, 6) concerns about the well-being of infants, 7) cultural perspectives, and 8) encouragement by trusted supporters. Conclusion Findings suggest that reliable information, social support, and trusted doctors’ advice can motivate COVID-19 vaccination. However, barriers such as misinformation, mistrust in the health care system, and fears related to potential side effects impede vaccination uptake among AA and Hispanic pregnant and postpartum women. Future interventions should target these barriers, along with health disparities, involve trusted doctors in outreach, and initiate vaccine conversations to promote vaccination among this population.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.20.23292951v1" target="_blank">Factors influencing COVID-19 vaccination decision-making among African American and Hispanic pregnant and postpartum women in Deep South</a>
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<li><strong>Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid</strong> -
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<div>
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The N-terminal (NTD) and the C-terminal (CTD) domains comprises the structure of the SARS-CoV-2 Nucleocapsid (N) protein. Crystal structure of the SARS-CoV-2 N protein determined by Kang et al, 2020, reveals the N-terminal RNA binding domain as a unique drug binding site. The present study targets this unique pocket with identified antivirals using structure-based drug repurposing approach. The high-affinity binding of potential molecules was characterised thermodynamically using Isothermal titration calorimetry. The selected molecules showed an inhibitory RNA binding potential between 8.8 micromolar and 15.7 micromolar IC50 when evaluated with a fluorescent-based assay. Furthermore, in an in vitro cell-based antiviral assay, these ten antiviral molecules demonstrated high effectiveness in halting SARS-CoV-2 replication. Telmisartan and BMS-189453, the two highly potent antivirals, have ~0.98 micromolar and 1.02 micromolar EC50 values with the selective index of >102, and >98, respectively. For the first time, this study presents drug molecules specifically targeting the NTD of SARS-CoV-2, offering essential insights for the development of therapeutic interventions against this virus, which is still a potential global threat to public health.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.03.12.484092v4" target="_blank">Mechanistic and thermodynamic characterization of antivirals targeting druggable pocket of SARS-CoV-2 nucleocapsid</a>
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<li><strong>Impact of Emerging COVID-19 variants on psychosocial health: A Systematic Review</strong> -
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Background: The COVID-19 pandemic has had significant psychological effects on individuals and communities around the world. Studies have found that the prevalence of anxiety and depression symptoms increased significantly during the pandemic. The goal of the study is to understand how the emerging new virus variants keep the world in a state of fear and the ways in which mental health measures can be implemented and adopted to alleviate anxiety. Methods: A broad search for observational studies were carried out in Pubmed, Google Scholar, Clinical Key, and World Medical Library. Studies that reported and/or related the existence of anxiety generated by suffering or not from diseases caused by the new emerging Covid-19 viruses and that for which the full text of the article was accessible were included in the study while systematic review and meta-analysis and studies in groups were excluded. Results: 22 studies were included in the review. The deleterious psychosocial effects were the restructuring of life, establishment of unhealthy habits, emergence of “corona phobia”, fear and stigma of being afflicted with the disease and spreading it to loved ones, and lack of contact with others. Increased rates of depression and anxiety were also seen. The circulating variants responsible for these main psychosocial repercussions were: Epsilon, Zeta, Eta, Iota, Kappa, Alpha, Beta, Gamma, and Delta. Social support was found to be protective. Conclusion: Hence interventions targeted at promoting mental health should be considered a public health priority.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.23.23293040v1" target="_blank">Impact of Emerging COVID-19 variants on psychosocial health: A Systematic Review</a>
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<li><strong>Genomic Analysis and Surveillance of Respiratory Syncytial Virus (RSV) Using Wastewater-Based Epidemiology (WBE)</strong> -
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Respiratory syncytial virus (RSV) causes severe infections in infants, immunocompromised or elderly individuals resulting in annual epidemics of respiratory disease. Currently, limited clinical RSV surveillance and the lack of predictable RSV seasonal dynamics and limits the public health response. Wastewater-based epidemiology (WBE) has the capacity to determine levels of health-associated biomarkers and has recently been used globally as a key metric in determining prevalence of SARS-CoV-2 in the community. However, the application of genomic WBE for the surveillance of other respiratory viruses is limited. In this study, we present an integrated genomic WBE approach, using RT-qPCR and partial sequencing of the G gene to monitor RSV levels and variants in the community across 2 years encompassing two periods of high RSV clinical positivity in Northern Ireland. We report increasing detection of RSV in wastewater concomitant with increasing numbers of RSV positive clinical cases. Furthermore, analysis of wastewater-derived RSV sequences permitted subtyping, genotyping, and identification of distinct circulating lineages within and between seasons. Altogether, our genomic WBE platform has the potential to complement ongoing global surveillance efforts and aid the management of RSV by informing the timely deployment of pharmaceutical and non-pharmaceutical interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.21.23293016v1" target="_blank">Genomic Analysis and Surveillance of Respiratory Syncytial Virus (RSV) Using Wastewater-Based Epidemiology (WBE)</a>
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<li><strong>Incubation-period estimates of Omicron (BA.1) variant from Taiwan, December 2021-January 2022, and its comparison to other SARS-CoV-2 variants: a statistical modeling, systematic search and meta-analysis</strong> -
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Background: The ongoing COVID-19 pandemic has seen several variants of concern, including the Omicron (BA.1) variant which emerged in October 2021. Accurately estimating the incubation period of these variants is crucial for predicting disease spread and formulating effective public health strategies. However, existing estimates often conflict because of biases arising from the dynamic nature of epidemic growth and selective inclusion of cases. This study aims to accurately estimate of the Omicron (BA.1) variant incubation period based on data from Taiwan, where disease incidence remained low and contact tracing was comprehensive during the first months of the Omicron outbreak. Methods: We reviewed 100 contact-tracing records for cases of the Omicron BA.1 variant reported between December 2021 and January 2022, and found enough information to analyze 70 of these. The incubation period distribution was estimated by fitting data on exposure and symptom onset within a Bayesian mixture model using gamma, Weibull, and lognormal distributions as candidates. Additionally, a systematic literature search was conducted to accumulate data for estimates of the incubation period for Omicron (BA.1/2, BA.4/5) subvariants, which was then used for meta-analysis and comparison. Results: The mean incubation period was estimated at 3.5 days (95% credible interval: 3.1-4.0 days), with no clear differences when stratified by vaccination status or age. This estimate aligns closely with the pooled mean of 3.4 days (3.0-3.8 days) obtained from a meta-analysis of other published studies on Omicron subvariants. Conclusions: The relatively shorter incubation period of the Omicron variant, as compared to previous SARS-CoV2 variants, implies its potential for rapid spread but also opens the possibility for individuals to voluntarily adopt shorter, more resource-efficient quarantine periods. Continual updates to incubation period estimates, utilizing data from comprehensive contact tracing, are crucial for effectively guiding these voluntary actions and adjusting high socio-economic cost interventions.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.20.23292983v1" target="_blank">Incubation-period estimates of Omicron (BA.1) variant from Taiwan, December 2021-January 2022, and its comparison to other SARS-CoV-2 variants: a statistical modeling, systematic search and meta-analysis</a>
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<li><strong>Artificial Intelligence in Biomedicine: Systematic Review</strong> -
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Abstract Artificial Intelligence (AI) is a rapidly progressing technology with its applications expanding exponentially over the past decade. While initial breakthroughs predominantly focused on deep learning and computer vision, recent advancements have facilitated a shift towards natural language processing and beyond. This includes generative models, like ChatGPT, capable of understanding the 9grammar9 of software code, analog signals, and molecular structures. This research undertakes a comprehensive examination of AI trends within the biomedical domain, including the impact of ChatGPT. We explore scientific literature, clinical trials, and FDA-approval data, utilizing a thematic synthesis approach and bibliometric mapping of keywords to examine numerous subsets from over a hundred thousand unique records found in prominent public repositories up to mid- July 2023. Our analysis reveals a higher prevalence of general health-related publications compared to more specialized papers using or evaluating ChatGPT. However, the growth in specialized papers suggests a convergence with the trend observed for other AI tools. Our findings also imply a greater prevalence of publications using ChatGPT across multiple medical specialties compared to other AI tools, indicating its rising influence in complex fields requiring interdisciplinary collaboration. Leading topics in AI literature include radiology, ethics, drug discovery, COVID-19, robotics, brain research, stroke, and laparoscopy, indicating a shift from laboratory to emergency medicine and deep-learning-based image processing. Publications involving ChatGPT predominantly address current themes such as COVID-19, practical applications, interdisciplinary collaboration, and risk mitigation. Radiology retains dominance across all stages of biomedical R&D, spanning preprints, peer-reviewed papers, clinical trials, patents, and FDA approvals. Meanwhile, surgery-focused papers appear more frequently within ChatGPT preprints and case reports. Traditionally less represented areas, such as Pediatrics, Otolaryngology, and Internal Medicine, are starting to realize the benefits of ChatGPT, hinting at its potential to spark innovation within new medical sectors. AI application in geriatrics is notably underrepresented in publications. However, ongoing clinical trials are already exploring the use of ChatGPT for managing age-related conditions. The higher frequency of general health-related publications compared to specialized papers employing or evaluating ChatGPT showcases its broad applicability across multiple fields. AI, particularly ChatGPT, possesses significant potential to reshape the future of medicine. With millions of papers published annually across various disciplines, efficiently navigating the information deluge to pinpoint valuable studies has become increasingly challenging. Consequently, AI methods, gaining in popularity, are poised to redefine the future of scientific publishing and its educational reach. Despite challenges like quality of training data and ethical concerns, prevalent in preceding AI tools, the wider applicability of ChatGPT across diverse fields is manifest. This review employed the PRISMA tool and numerous overlapping data sources to minimize bias risks.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.23.23292672v1" target="_blank">Artificial Intelligence in Biomedicine: Systematic Review</a>
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<li><strong>Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK</strong> -
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Background The continued emergence of SARS-CoV-2 variants of concern (VOC) requires timely analytical and clinical evaluation of antigen-based rapid diagnostic tests (Ag-RDTs) especially those that are recommended for at home use. Methods The limit of detection (LOD) of 34 Ag-RDTs was evaluated using the most encountered SARS-CoV-2 VOC viral isolates (Alpha, Delta, Gamma, Omicron BA.1, Omicron BA.5) and the wild type (WT). Clinical sensitivity was further evaluated for five Ag-RDT utilising retrospective samples (Alpha, Delta, Omicron BA.1) and one Ag-RDT utilising prospective clinical samples (Delta and Omicron BA.1). Findings For the WT, Alpha, Delta, Gamma and Omicron (BA.1) variants 22, 32, 29, 31 and 32 of the 34 Ag-RDTs evaluated met the World Health Organisations (WHO) target product profile (TPP), respectively. Of the 31 Ag-RDTs included for Omicron BA.5 evaluation 29 met the WHO TPP. Additionally, the LODs for samples spiked with Omicron BA.5 were significantly lower than all other VOCs included (p<0.001). In the retrospective clinical evaluation when comparing RNA copies/mL, the Ag-RDTs detected Alpha and Omicron (BA.1) more sensitively than the Delta VOC. Samples with high RT-qPCR Cts (Ct>25) resulted in reduced test sensitivities across all variants. We used linear regression to model the 50% and 95% LOD of clinical samples and observed statistically similar results for all tests. In the prospective clinical samples, the sensitivity was statistically similar for the Delta VOC 71.9% (CI 95% 53.3-86.6%) and Omicron VOC 84.4% (CI95% 75.3-91.2%). Interpretation Test performance differs between SARS-CoV-2 VOCs, and high sensitivity was achieved when testing the Omicron BA.5 VOC compared to the WHO Ag-RDT requirements. Continuous evaluations must be performed to monitor test performance.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.24.23293072v1" target="_blank">Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK</a>
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<li><strong>Reactivation of herpesvirus type-6 and IgA/IgM-mediated responses to activin-A underpin Long COVID, including affective symptoms and chronic fatigue syndrome.</strong> -
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Background: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in Long COVID. Objectives: To investigate whether Long COVID and depressive, anxiety and chronic fatigue syndrome (CFS) symptoms, are associated with IgA/IgM/IgG to SARS-CoV-2, human Herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. Methods: We examined 90 Long COVID patients and 90 healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). Results: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6 and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the Long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve=0.876); the topmost predictors were: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top-5 predictors of affective symptoms due to Long COVID were: IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r=0.636). The top-5 predictors of CFS due to Long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r=0.709). Conclusion: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of Long COVID as well as the severity of affective symptoms and CFS due to Long COVID.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.07.23.23293046v1" target="_blank">Reactivation of herpesvirus type-6 and IgA/IgM-mediated responses to activin-A underpin Long COVID, including affective symptoms and chronic fatigue syndrome.</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>Smell in COVID-19 and Efficacy of Nasal Theophylline (SCENT 3)</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: theophylline; Drug: Placebo<br/><b>Sponsor</b>: Washington University School of Medicine<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>Lymph Node Aspiration to Decipher the Immune Response of Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine.</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Procedure: Lymph node aspiration / Blood sampling<br/><b>Sponsor</b>: Assistance Publique - Hôpitaux de Paris<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>COVID-19 Trial of the Candidate Vaccine MVA-SARS-2-S in Adults</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: MVA-SARS-2-S; Other: Placebo<br/><b>Sponsors</b>: Universitätsklinikum Hamburg-Eppendorf; German Center for Infection Research; Philipps University Marburg Medical Center; Ludwig-Maximilians - University of Munich; University Hospital Tuebingen; CTC-NORTH<br/><b>Withdrawn</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>Immunoadsorption vs. Sham Treatment in Post COVID-19 Patients With Chronic Fatigue Syndrome</strong> - <b>Conditions</b>: Fatigue; Post-Acute COVID-19 Syndrome<br/><b>Intervention</b>: Procedure: Immunoadsorption vs. sham immunoadsorption<br/><b>Sponsor</b>: Hannover Medical School<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>Non-ventilated Prone Positioning in the COVID-19 Population</strong> - <b>Conditions</b>: COVID-19; Proning; Oxygenation; Length of Stay<br/><b>Interventions</b>: Other: Proning group; Other: Control group<br/><b>Sponsor</b>: Baylor St. Luke’s 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>Treatment of Long COVID (TLC) Feasibility Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: Low-dose Naltrexone (LDN); Drug: Cetirizine; Drug: Famotidine; Drug: LDN Placebo; Drug: Cetirizine Placebo; Drug: Famotidine Placebo<br/><b>Sponsors</b>: Emory University; CURE Drug Repurposing Collaboratory (CDRC)<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>Safety, Efficacy, and Dosing of VIX001 in Patients With Neurological Symptoms of Post Acute COVID-19 Syndrome (PACS).</strong> - <b>Conditions</b>: Post-Acute COVID-19 Syndrome; Cognitive Impairment; Neurological Complication<br/><b>Intervention</b>: Drug: VIX001<br/><b>Sponsor</b>: Neobiosis, LLC<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>PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Drug: Upamostat; Drug: Placebo (PO)<br/><b>Sponsors</b>: Henry M. Jackson Foundation for the Advancement of Military Medicine; Joint Program Executive Office Chemical, Biological, Radiological, and Nuclear Defense Enabling Biotechnologies; FHI Clinical, Inc.; RedHill Biopharma Limited<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Efficacy, Safety, Tolerability and PK of SNS812 in Mild to Moderate COVID-19 Patients</strong> - <b>Condition</b>: Disease Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (Disorder)<br/><b>Interventions</b>: Drug: MBS-COV; Drug: Placebo<br/><b>Sponsor</b>: Oneness Biotech 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>A Clinical Evaluation of the Safety and Efficacy of Randomized Placebo Versus the 8-aminoquinoline Tafenoquine for Early Symptom Resolution in Patients With Mild to Moderate COVID 19 Disease and Low Risk of Disease Progression</strong> - <b>Conditions</b>: COVID 19 Disease; Mild to Moderate COVID 19 Disease; SARS-CoV-2; Infectious Disease; Severe Acute Respiratory Syndrome Coronavirus 2<br/><b>Interventions</b>: Drug: Tafenoquine Oral Tablet; Drug: Placebo<br/><b>Sponsor</b>: 60P Australia Pty Ltd<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy of the Therapy With BRAINMAX® Using fMRI for the Treatment of Patients With Asthenia After COVID-19</strong> - <b>Conditions</b>: Asthenia; COVID-19; Functional MRI; Cognitive Impairment<br/><b>Interventions</b>: Other: Structural and functional MRI; Drug: Ethyl methyl hydroxypyridine succinate + Meldonium; Drug: Placebo<br/><b>Sponsor</b>: Promomed, LLC<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NDV-HXP-S Vaccine Clinical Trial (COVIVAC)</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: COVIVAC vaccine<br/><b>Sponsors</b>: Institute of Vaccines and Medical Biologicals, Vietnam; National Institute of Hygiene and Epidemiology (NIHE), Vietnam; Center for Disease Control of Thai Binh Province, Vietnam<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MR-spectroscopy in Post-covid Condition Prior to and Following a Yoga Breathing Intervention</strong> - <b>Conditions</b>: Post COVID-19 Condition; Somatic Symptom Disorder<br/><b>Interventions</b>: Behavioral: yoga; Behavioral: social contact<br/><b>Sponsor</b>: Medical University Innsbruck<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>Clinical Evaluation of SARS-COV-2 (COVID-19), Influenza and RSV 8-Well MT-PCR Panel for In Vitro Diagnostics</strong> - <b>Condition</b>: Respiratory Viral Infection<br/><b>Interventions</b>: Diagnostic Test: SARS-COV-2, Influenza and RSV 8-Well MT-PCR Panel; Diagnostic Test: BioFire Respiratory Panel 2.1<br/><b>Sponsor</b>: AusDiagnostics Pty Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Expressive Interviewing Agents to Support Health-Related Behavior Change</strong> - <b>Condition</b>: Mental Stress<br/><b>Intervention</b>: Other: Expressive Interviewing<br/><b>Sponsors</b>: University of Michigan; University of Texas at Austin<br/><b>Completed</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>Korean Red Ginseng Relieves Inflammation and Modulates Immune Response Induced by Pseudo-Type SARS-CoV-2</strong> - Few studies have reported the therapeutic effects of Korean red ginseng (KRG) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the positive effects of KRG on other viruses have been reported and the effects of KRG on pulmonary inflammatory diseases have also been studied. Therefore, this study investigated the therapeutic effects of KRG-water extract (KRG-WE) in a pseudo-type SARS-CoV-2 (PSV)-induced lung injury model. Constructing the pseudovirus, human…</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>Vector-delivered artificial miRNA effectively inhibits Porcine epidemic diarrhea virus replication</strong> - CONCLUSIONS: In summary, these results suggest that an RNAi based on amiRNA targeting the conserved region of the virus is an effective method to improve PEDV nucleic acid inhibitors and provide a novel treatment strategy for PEDV infection.</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>Deciphering the role of fucoidan from brown macroalgae in inhibiting SARS-CoV-2 by targeting its main protease and receptor binding domain: Invitro and insilico approach</strong> - The current study investigated the role of fucoidan from Padina tetrastromatica and Turbinaria conoides against 3-chymotrypsin like protease (3CL^(pro)) and receptor binding domain (RBD) spike protein of SARS-CoV-2 using an invitro and computational approach. The 3CL^(pro) and RBD genes were successfully cloned in pET28a vector, expressed in BL-21DE3 E. coli rosetta cells and purified by ion exchange affinity and size exclusion chromatography. Fucoidan extracted from both biomass using green…</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>Inactivated SARS-CoV-2 booster vaccine enhanced immune responses in patients with chronic liver diseases</strong> - Chronic liver disease (CLD) entails elevated risk of COVID-19 severity and mortality. The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear. Therefore, we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls (HC) to analyze neutralizing antibodies (NAbs) against SARS-CoV-2 prototype and BA.4/5 variant, anti-receptor binding domain (RBD) IgG, and total anti-SARS-CoV-2 antibodies….</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 kynurenine pathway of tryptophan metabolism: a neglected therapeutic target of COVID-19 pathophysiology and immunotherapy</strong> - SARS-CoV-2 (COVID-19) exerts profound changes in the kynurenine (Kyn) pathway (KP) of tryptophan (Trp) metabolism that may underpin its pathophysiology. The KP is the main source of the vital cellular effector NAD+ and intermediate metabolites that modulate immune and neuronal functions. Trp metabolism is the top pathway influenced by COVID-19. Sixteen studies established virus-induced activation of the KP mediated mainly by induction of indoleamine 2,3-dioxygenase (IDO1) in most affected…</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>Regulation of autophagy by SARS-CoV-2: The multifunctional contributions of ORF3a</strong> - Severe acute respiratory syndrome-coronavirus-1 (SARS-CoV-2) regulates autophagic flux by blocking the fusion of autophagosomes with lysosomes, causing the accumulation of membranous vesicles for replication. Multiple SARS-CoV-2 proteins regulate autophagy with significant roles attributed to ORF3a. Mechanistically, open reading frame 3a (ORF3a) forms a complex with UV radiation resistance associated, regulating the functions of the PIK3C3-1 and PIK3C3-2 lipid kinase complexes, thereby…</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>Fangchinoline inhibits the PEDV replication in intestinal epithelial cells via autophagic flux suppression</strong> - Animal and human health are severely threatened by coronaviruses. The enteropathogenic coronavirus, porcine epidemic diarrhea virus (PEDV), is highly contagious, leading to porcine epidemic diarrhea (PED), which causes large economic losses in the world’s swine industry. Piglets are not protected from emerging PEDV variants; therefore, new antiviral measures for PED control are urgently required. Herein, the anti-PEDV effects and potential mechanisms of fangchinoline (Fan) were investigated. Fan…</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>Silver N-heterocyclic carbene complexes are potent uncompetitive inhibitors of the papain-like protease with antiviral activity against SARS-CoV-2</strong> - The ongoing SARS-CoV-2 pandemic has caused a high demand for novel innovative antiviral drug candidates. Despite promising results, metal complexes have been relatively unexplored as antiviral agents in general and in particular against SARS-CoV-2. Here we report on silver NHC complexes with chloride or iodide counter ligands that are potent inhibitors of the SARS-CoV-2 papain-like protease (PL^(pro)) but inactive against 3C-like protease (3CL^(pro)) as another SARS-CoV-2 protease. Mechanistic…</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>Nanoparticle approaches for the renin-angiotensin system</strong> - The renin-angiotensin system (RAS) is a hormonal cascade that contributes to several disorders: systemic hypertension, heart failure, kidney disease, and neurodegenerative disease. Activation of the RAS can promote inflammation and fibrosis. Drugs that target the RAS can be classified into 3 categories, AT1 angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and renin inhibitors. The therapeutic efficacy of current RAS-inhibiting drugs is limited by poor…</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>Natural fucoidans inhibit coronaviruses by targeting viral spike protein and host cell furin</strong> - Fucoidans are a class of long chain sulfated polysaccharides and have multiple biological functions. Herein, four natural fucoidans extracted from Fucus vesiculosus, F. serratus, Laminaria japonica and Undaria pinnatifida, were tested for their HCoV-OC43 inhibition and found to demonstrate EC(50) values ranging from 0.15 to 0.61 µg/mL. That from U. pinnatifida exhibited the most potent anti-HCoV-OC43 activity with an EC(50) value of 0.15 ± 0.02 µg/mL, a potency largely independent of its sulfate…</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>One master and two servants: One Zr(Ⅳ) with two ligands of TCPP and NH<sub>2</sub>-BDC form the MOF as the electrochemiluminescence emitter for the biosensing application</strong> - Here we put forward an innovative “one master and two servants” strategy for enhancing the ECL performance. A novel ECL luminophore named Zr-TCPP/NH(2)-BDC (TCPP@UiO-66-NH(2)) was synthesized by self-assembly of meso-tetra(4-carboxyphenyl)porphine (TCPP) and 4-aminobenzoic acid (NH(2)-BDC) with Zr clusters. TCPP@UiO-66-NH(2) has a porous structure and a highly ordered structure, which allows the molecular motion of TCPP to be effectively confined, thereby inhibiting nonradiative energy transfer….</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications</strong> - Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer. These ionizable lipids have unique…</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 and validation of fusidic acid and flufenamic acid as inhibitors of SARS-CoV-2 replication using DrugSolver CavitomiX</strong> - In this work, we present DrugSolver CavitomiX, a novel computational pipeline for drug repurposing and identifying ligands and inhibitors of target enzymes. The pipeline is based on cavity point clouds representing physico-chemical properties of the cavity induced solely by the protein. To test the pipeline’s ability to identify inhibitors, we chose enzymes essential for SARS-CoV-2 replication as a test system. The active-site cavities of the viral enzymes main protease (M^(pro)) and papain-like…</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>Antibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants</strong> - Emerging SARS-CoV-2 variants, notably Omicron, continue to remain a formidable challenge to worldwide public health. The SARS-CoV-2 receptor-binding domain (RBD) is a hotspot for mutations, reflecting its critical role at the ACE2 interface during viral entry. Here, we comprehensively investigated the impact of RBD mutations, including 5 variants of concern (VOC) or interest-including Omicron (BA.2)-and 33 common point mutations, both on IgG recognition and ACE2-binding inhibition, as well as…</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 quantum chemical study on the anti-SARS-CoV-2 activity of TMPRSS2 inhibitors</strong> - Nafamostat and camostat are known to inhibit the spike protein-mediated fusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by forming a covalent bond with the human transmembrane serine protease 2 (TMPRSS2) enzyme. Previous experiments revealed that the TMPRSS2 inhibitory activity of nafamostat surpasses that of camostat, despite their structural similarities; however, the molecular mechanism of TMPRSS2 inhibition remains elusive. Herein, we report the energy profiles of the…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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