Daily-Dose/archive-covid-19/12 February, 2023.html

184 lines
52 KiB
HTML
Raw Normal View History

2023-02-12 12:47:47 +00:00
<!DOCTYPE html>
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
<meta charset="utf-8"/>
<meta content="pandoc" name="generator"/>
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
<title>12 February, 2023</title>
<style>
code{white-space: pre-wrap;}
span.smallcaps{font-variant: small-caps;}
span.underline{text-decoration: underline;}
div.column{display: inline-block; vertical-align: top; width: 50%;}
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
ul.task-list{list-style: none;}
</style>
<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>
<body>
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
<ul>
<li><a href="#from-preprints">From Preprints</a></li>
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
<li><a href="#from-pubmed">From PubMed</a></li>
<li><a href="#from-patent-search">From Patent Search</a></li>
</ul>
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
<ul>
<li><strong>GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</strong> -
<div>
Human pluripotent stem cell (hPSC)-derived tissues can be used to model diseases and validate targets in cell types that are challenging to harvest and study at scale, such as neutrophils. Neutrophil dysregulation, specifically unbalanced neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. hPSCs can provide a limitless supply of neutrophils (iNeutrophils) to study these processes and discover and validate targets in vitro. However, current iNeutrophil differentiation protocols are inefficient and generate heterogeneous cultures consisting of different granulocytes and precursors, which can confound the study of neutrophil biology. Here, we describe a method to dramatically improve iNeutrophils yield, purity, functionality, and maturity through the deletion of the transcription factor GATA1. GATA1 knockout (KO) iNeutrophils are nearly identical to primary neutrophils in cell surface marker expression, morphology, and host defense functions. Unlike wild type (WT) iNeutrophils, GATA1 KO iNeutrophils generate NETs in response to the physiologic stimulant lipid polysaccharide (LPS), suggesting they could be used as a more accurate model when performing small-molecule screens to find NET inhibitors. Furthermore, we demonstrate that GATA1 KO iNeutrophils are a powerful tool in quickly and definitively determining involvement of a given protein in NET formation.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.08.526339v1" target="_blank">GATA1 knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation</a>
</div></li>
<li><strong>Long COVID in Elderly Patients: An Epidemiologic Exploration Using a Medicare Cohort</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Incidence of long COVID in the elderly is difficult to estimate and can be under-reported. While long COVID is sometimes considered a novel disease, many viral or bacterial infections have been known to cause prolonged illnesses. We postulate that some influenza patients might develop residual symptoms that would satisfy the diagnostic criteria for long COVID, a condition we call “long Flu”. In this study, we estimate the incidence of long COVID and long Flu among Medicare patients using the World Health Organization (WHO) consensus definition. We compare the incidence, symptomatology, and healthcare utilization between long COVID and long Flu patients.   Methods and Findings: This is a cohort study of Medicare (the U.S. federal health insurance program) beneficiaries over 65. ICD-10-CM codes were used to capture COVID-19, influenza and residual symptoms. Long COVID was identified by a) the designated long COVID-19 code B94.8 (code-based definition), or b) any of 11 symptoms identified in the WHO definition (symptom-based definition), from one to 3 months post infection. A symptom would be excluded if it occurred in the year prior to infection. Long Flu was identified in influenza patients from the combined 2018 and 2019 Flu seasons by the same symptom-based definition for long COVID. Long COVID and long Flu were compared in four outcome measures: a) hospitalization (any cause), b) hospitalization (for long COVID symptom), c) emergency department (ED) visit (for long COVID symptom), and d) number of outpatient encounters (for long COVID symptom), adjusted for age, sex, race, region, Medicare-Medicaid dual eligibility status, prior-year hospitalization, and chronic comorbidities. Among 2,071,532 COVID-19 patients diagnosed between April 2020 and June 2021, symptom-based definition identified long COVID in 16.6% (246,154/1,479,183) and 29.2% (61,631/210,765) of outpatients and inpatients respectively. The designated code gave much lower estimates (outpatients 0.49% (7,213/1,479,183), inpatients 2.6% (5,521/210,765)). Among 933,877 influenza patients, 17.0% (138,951/817,336) of outpatients and 24.6% (18,824/76,390) of inpatients fit the long Flu definition. Long COVID patients had higher incidence of dyspnea, fatigue, palpitations, loss of taste/smell and neurocognitive symptoms compared to long Flu. Long COVID outpatients were more likely to have any-cause hospitalization (31.9% (74,854/234,688) vs. 26.8% (33,140/123,736), odds ratio 1.06 (95% CI 1.05-1.08, p&lt;0.001)), and more outpatient visits than long Flu outpatients (mean 2.9(SD 3.4) vs. 2.5(SD 2.7) visits, incidence rate ratio 1.09 (95% CI 1.08-1.10, p&lt;0.001)). There were less ED visits in long COVID patients, probably because of reduction in ED usage during the pandemic. The main limitation of our study is that the diagnosis of long COVID in is not independently verified.   Conclusions: Relying on specific long COVID diagnostic codes results in significant under-reporting. We observed that about 30% of hospitalized COVID-19 patients developed long COVID. In a similar proportion of patients, long COVID-like symptoms (long Flu) can be observed after influenza, but there are notable differences in symptomatology between long COVID and long Flu. The impact of long COVID on healthcare utilization is higher than long Flu.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285742v1" target="_blank">Long COVID in Elderly Patients: An Epidemiologic Exploration Using a Medicare Cohort</a>
</div></li>
<li><strong>Functional comparisons of the virus sensor RIG-I from humans, the microbat Myotis daubentonii, and the megabat Rousettus aegyptiacus, and their response to SARS-CoV-2 infection</strong> -
<div>
Bats (order Chiroptera) are a major reservoir for emerging and re-emerging zoonotic viruses. Their tolerance towards highly pathogenic human viruses led to the hypothesis that bats may possess an especially active antiviral interferon (IFN) system. Here, we cloned and functionally characterized the virus RNA sensor, Retinoic Acid-Inducible Gene-I (RIG-I), from the “microbat” Myotis daubentonii (suborder Yangochiroptera) and the “megabat” Rousettus aegyptiacus (suborder Yinpterochiroptera), and compared them to the human ortholog. Our data show that the overall sequence and domain organization is highly conserved and that all three RIG-I orthologs can mediate a similar IFN induction in response to viral RNA at 37{degrees} and 39{degrees}C, but not at 30{degrees}C. Like human RIG-I, bat RIG-Is were optimally activated by double stranded RNA containing a 5-triphosphate end and required Mitochondrial Antiviral-Signalling Protein (MAVS) for antiviral signalling. Moreover, the RIG-I orthologs of humans and of R. aegyptiacus, but not of M. daubentonii, enable innate immune sensing of SARS-CoV-2 infection. Our results thus show that microbats and megabats express a RIG-I that is not substantially different from the human counterpart with respect to function, temperature dependency, antiviral signaling, and RNA ligand properties, and that human and megabat RIG-I are able to sense SARS-CoV-2 infection.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.08.527785v1" target="_blank">Functional comparisons of the virus sensor RIG-I from humans, the microbat Myotis daubentonii, and the megabat Rousettus aegyptiacus, and their response to SARS-CoV-2 infection</a>
</div></li>
<li><strong>Defining Cities in the New Normal: A Conjoint Experiment of Livability Attributes</strong> -
<div>
This paper examines attributes of cities that people prefer to live in after the outbreak of the COVID-19. Using an online survey of approximately 700 respondents in the Philippines conducted from December 2020 to March 2021 that incorporated conjoint experiments, we investigate the relative importance of various attributes of a city such as neighborhood, healthcare, infrastructure, and governance in influencing peoples willingness to live in the city under the new normal.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/a7ezj/" target="_blank">Defining Cities in the New Normal: A Conjoint Experiment of Livability Attributes</a>
</div></li>
<li><strong>Population genetics in the early emergence of the Omicron SARS-CoV-2 variant in the provinces of South Africa.</strong> -
<div>
Population genetic analyses of viral genome populations provide insight into the emergence and evolution of new variants of SARS-CoV-2. In this study, we use a population genetic approach to examine the evolution of the Omicron variant of SARS-CoV-2 in four provinces of South Africa (Eastern Cape, Gauteng, KwaZulu-Natal, and Mpumalanga) during the first months before emergence and after early spread. Our results show that Omicron polymorphisms increase sharply from September to November. We found differences between SARS-CoV-2 populations from Gauteng and Kwazulu-Natal and viruses from the Eastern Cape, where allele frequencies were higher, suggesting that natural selection may have contributed to the increase in frequency or that this was the site of origin. We found that the frequency of variants N501Y, T478K, and D614G increased in the spike in November compared with other mutations, some of which are also present in other animal hosts. Gauteng province was the most isolated, and most genetic variation was found within populations. Our population genomic approach is useful for small-scale genomic surveillance and identification of novel allele-level variants that can help us understand how SARS-CoV-2 will continue to adapt to humans and other hosts.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.09.527920v1" target="_blank">Population genetics in the early emergence of the Omicron SARS-CoV-2 variant in the provinces of South Africa.</a>
</div></li>
<li><strong>Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p</strong> -
<div>
The stem loop 2 motif (s2m), a highly conserved 41-nucleotide hairpin structure in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, serves as an attractive therapeutic target that may have important roles in the virus life cycle or interactions with the host. However, the conserved s2m in Delta SARS-CoV-2, a previously dominant variant characterized by high infectivity and disease severity, has received relatively less attention than that of the original SARS-CoV-2 virus. The focus of this work is to identify and define the s2m changes between Delta and SARS-CoV-2 and subsequent impact of those changes upon the s2m dimerization and interactions with the host microRNA miR-1307-3p. Bioinformatics analysis of the GISAID database targeting the s2m element reveals a greater than 99% correlation of a single nucleotide mutation at the 15th position (G15U) in Delta SARS-CoV-2. Based on 1H NMR assignments comparing the imino proton resonance region of s2m and the G15U at 19{degrees}C, we find that the U15-A29 base pair closes resulting in a stabilization of the upper stem without overall secondary structure deviation. Increased stability of the upper stem did not affect the chaperone activity of the viral N protein, as it was still able to convert the kissing dimers formed by s2m G15U into a stable duplex conformation, consistent with the s2m reference. However, we find that the s2m G15U mutation drastically reduces the binding affinity of the host miR-1307-3p. These findings demonstrate that the observed G15U mutation alters the secondary structure of s2m with subsequent impact on viral binding of host miR-1307-3p, with potential consequences on the immune response.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528014v1" target="_blank">Effect of the SARS-CoV-2 Delta-associated G15U mutation on the s2m element dimerization and its interactions with miR-1307-3p</a>
</div></li>
<li><strong>Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2</strong> -
<div>
Analyses of the genomic diversity of SARS-CoV-2 found that some sites across the genome appear to have mutated independently multiple times with frequency significantly higher than four-fold sites, which can be either due to mutational bias, i.e., elevated mutation rate in some sites of the genome, or selection of the variants due to antagonistic pleiotropy, a condition where mutations increase some components of fitness at a cost to others. To examine how different forces shaped evolution of SARS-CoV-2 in 2020-2021, we analyzed a large set of genome sequences (~ 2 million). Here we show that while evolution of SARS-CoV-2 during the pandemic was largely mutation-driven, a group of nonsynonymous changes is probably maintained by antagonistic pleiotropy. To test this hypothesis, we studied the function of one such mutation, spike M1237I. Spike I1237 increases viral assembly and secretion, but decreases efficiency of transmission in vitro. Therefore, while the frequency of spike M1237I may increase within hosts, viruses carrying this mutation would be outcompeted at the population level. We also discuss how the antagonistic pleiotropy might facilitate positive epistasis to promote virus adaptation and reconcile discordant estimates of SARS-CoV-2 transmission bottleneck sizes in previous studies.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.527437v1" target="_blank">Antagonistic pleiotropy plays an important role in governing the evolution and genetic diversity of SARS-CoV-2</a>
</div></li>
<li><strong>Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2</strong> -
<div>
Long COVID (LC), a type of post-acute sequelae of SARS-CoV-2 infection (PASC), occurs after at least 10% of SARS-CoV-2 infections, yet its etiology remains poorly understood. Here, we used multiple omics assays (CyTOF, RNAseq, Olink) and serology to deeply characterize both global and SARS-CoV-2-specific immunity from blood of individuals with clear LC and non-LC clinical trajectories, 8 months following infection and prior to receipt of any SARS-CoV-2 vaccine. Our analysis focused on deep phenotyping of T cells, which play important roles in immunity against SARS-CoV-2 yet may also contribute to COVID-19 pathogenesis. Our findings demonstrate that individuals with LC exhibit systemic inflammation and immune dysregulation. This is evidenced by global differences in T cell subset distribution in ways that imply ongoing immune responses, as well as by sex-specific perturbations in cytolytic subsets. Individuals with LC harbored increased frequencies of CD4+ T cells poised to migrate to inflamed tissues, and exhausted SARS-CoV-2-specific CD8+ T cells. They also harbored significantly higher levels of SARS-CoV-2 antibodies, and in contrast to non-LC individuals, exhibited a mis-coordination between their SARS-CoV-2-specific T and B cell responses. Collectively, our data suggest that proper crosstalk between the humoral and cellular arms of adaptive immunity has broken down in LC, and that this, perhaps in the context of persistent virus, leads to the immune dysregulation, inflammation, and clinical symptoms associated with this debilitating condition.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.09.527892v1" target="_blank">Long COVID manifests with T cell dysregulation, inflammation, and an uncoordinated adaptive immune response to SARS-CoV-2</a>
</div></li>
<li><strong>SARS-CoV-2 NSP5 Antagonizes the MHC II Antigen Presentation Pathway by Hijacking Histone Deacetylase 2</strong> -
<div>
The clearance of SARS-CoV-2 requires a multi-faceted immune response that is initiated by innate immune cells, with infection ultimately resolved by adaptive immune mechanisms. Induction of adaptive immunity to SARS-CoV-2 is dependent on the presentation of viral antigens on MHC II by professional antigen presenting cells such as dendritic cells and macrophages, to induce robust activation of CD4+ T cells. SARS-CoV-2 interferes with antigen presentation by downregulating MHC II on the antigen presenting cells of COVID-19 patients, but the molecular mechanism mediating this process is unelucidated. In this study, analysis of protein and gene expression in human antigen presenting cells reveals that the expression of MHC II is inhibited by the SARS-CoV-2 main protease, NSP5. Suppression of MHC II expression occurs via downregulation of the transcription factor CIITA, which is required for MHC II expression. This downregulation of CIITA is independent of NSP5s proteolytic activity, and rather, NSP5 delivers HDAC2 to the CIITA promoter via interactions with IRF3, Here, HDAC2 deacetylates and inactivates the CIITA promoter. This loss of CIITA expression prevents further expression of MHC II, with this suppression alleviated by ectopic expression of CIITA or knockdown of HDAC2. These results identify a novel mechanism by which SARS-CoV-2 can limit antigen presentation on MHC II, thereby delaying or weakening the subsequent adaptive immune response.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.02.10.528032v1" target="_blank">SARS-CoV-2 NSP5 Antagonizes the MHC II Antigen Presentation Pathway by Hijacking Histone Deacetylase 2</a>
</div></li>
<li><strong>Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico</strong> -
<div>
Over 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for &gt;12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.07.05.498834v3" target="_blank">Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico</a>
</div></li>
<li><strong>Age-specific severity of SARS-CoV-2 in February 2020 - June 2021 in the Netherlands</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Background: Severity of SARS-CoV-2 infection may vary over time. Here, we estimate age-specific risks of hospitalization, ICU admission and death given infection in the Netherlands from February 2020 - June 2021. Methods: A nationwide longitudinal serology study was used to estimate numbers of infections in three epidemic periods (February 2020 - June 2020, July 2020 - February 2021, March 2021 - June 2021). We accounted for reinfections and, as vaccination started in January 2021, breakthrough infections among vaccinated persons. Severity estimates were inferred by combining numbers of infections with aligned numbers of hospitalizations and ICU admissions from a national hospital-based registry, and aligned numbers of deaths based on national excess all-cause mortality estimates. Results: In each period there was a nearly consistent pattern of accelerating, almost exponential, increase in severity of infection with age. The rate of increase with age was highest for death and lowest for hospitalization. In the first period, the overall risk of hospitalization, ICU admission and death were 1.5% (95%-confidence interval [CI] 1.3-1.8%), 0.36% (95%-CI: 0.31-0.42%) and 1.2% (95%-CI: 1.0-1.4), respectively. The risk of hospitalization was higher in the following periods, while the risk of ICU admission remained stable. The risk of death decreased over time, with a substantial drop among ≥70-years-olds in February 2021 - June 2021. Conclusion: The accelerating increase in severity of SARS-CoV-2 with age remained intact during the first three epidemic periods in the Netherlands. The substantial drop in risk of death among elderly in the third period coincided with the introduction of COVID-19 vaccination.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285703v1" target="_blank">Age-specific severity of SARS-CoV-2 in February 2020 - June 2021 in the Netherlands</a>
</div></li>
<li><strong>Divergence of wastewater SARS-CoV-2 and reported laboratory-confirmed COVID-19 incident case data coincident with wide-spread availability of at-home COVID-19 antigen tests</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Concentrations of SARS-CoV-2 RNA in wastewater settled solids from publicly owned treatment works (POTWs) historically correlated strongly with laboratory confirmed incident COVID-19 case data. With the increased availability of at-home antigen tests since late 2021 and early 2022, laboratory test availability and test seeking behavior has decreased. In the United States, the results from at-home antigen tests are not typically reportable to public health agencies and thus are not counted in case reports. As a result, the number of reported laboratory-confirmed incident COVID-19 cases has decreased dramatically, even during times of increased test positivity rates and wastewater concentrations of SARS-CoV-2 RNA. Herein, we tested whether the correlative relationship between wastewater concentrations of SARS-CoV-2 RNA and reported laboratory-confirmed COVID-19 incidence rate has changed since 1 May 2022, a point in time immediately before the onset of the BA.2/BA.5 surge, the first surge to begin after at-home antigen test availability was high in the region. We used daily data from three POTWs in the Greater San Francisco Bay Area of California, USA for the analysis. We found that although there is a significant positive association between wastewater measurements and incident rate data collected after 1 May 2022, the parameters describing the relationship are different than those describing the relationship between the data collected prior to 1 May 2022. If laboratory test seeking or availability continues to change, the relationship between wastewater and reported case data will continue to change. Results suggests that, assuming SARS-CoV-2 RNA shedding remains relatively stable among those infected with the virus as different variants emerge, that wastewater concentrations of SARS-CoV-2 RNA can be used to estimate COVID-19 cases as they would have been during the time when laboratory testing availability and test seeking behavior were at a high (here, before 1 May 2022) using the historical relationship between SARS-CoV-2 RNA and COVID-19 case data.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285716v1" target="_blank">Divergence of wastewater SARS-CoV-2 and reported laboratory-confirmed COVID-19 incident case data coincident with wide-spread availability of at-home COVID-19 antigen tests</a>
</div></li>
<li><strong>Social deprivation and SARS-CoV-2 testing: a population-based analysis in a highly contrasted Southern France region</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
<b>Background</b>&lt;br&gt; Testing was the cornerstone of the COVID-19 epidemic response in most countries until vaccination became available for the general population. Social inequalities generally affect access to healthcare and health behaviours, and COVID-19 was rapidly shown to impact deprived population more drastically. In support of the regional health agency in Provence-Alpes-Cote d9Azur (PACA) in South-Eastern France, we analysed the relationship between testing rate and socio-demographic characteristics of the population, to identify gaps in testing coverage and improve targeting of response strategies. &lt;/br&gt; &lt;br&gt; <b>Methods</b>&lt;/br&gt;&lt;br&gt; We conducted an ecological analysis of SARS-CoV-2/COVID-19 testing rate in the PACA region, based on data aggregated at the finest spatial resolution available in France (IRIS) and by periods defined by public health implemented measures and major epidemiological changes. Using general census data, population density, and specific deprivation indices, we used principal component analysis followed by hierarchical clustering to define profiles describing local socio-demographic characteristics. We analysed the association between these profiles and testing rates in a generalized additive multilevel model, adjusting for access to healthcare, presence of a retirement home, and the age profile of the population. &lt;/br&gt; &lt;br&gt; <b>Results</b>&lt;/br&gt;&lt;br&gt; We identified 6 socio-demographic profiles across the 2,306 analysed IRIS spatial units: privileged, remote, intermediate, downtown, deprived and very deprived (ordered by increasing social deprivation index). Profiles also ranged from rural (remote) to high density urban areas (downtown, very deprived). From July 2020 to December 2021, we analysed SARS-CoV-2/COVID-19 testing rate over 10 periods. Testing rates fluctuated strongly but were highest in privileged and downtown areas, and lowest in very deprived ones. The lowest adjusted testing rate ratios (aTRR) between privileged (reference) and other profiles occurred after implementation of a mandatory healthpass for many leisure activities in July 2021. Periods of contextual testing near Christmas displayed the largest aTRR, especially during the last periods of 2021 after the end of free convenience testing for unvaccinated individuals.&lt;/br&gt; &lt;br&gt; <b>Conclusions</b>&lt;/br&gt;&lt;br&gt; We characterized in-depth local heterogeneity and temporal trends in testing rates and identified areas and circumstances associated with low testing rates, which the regional health agency targeted specifically for the deployment of health mediation activities.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285721v1" target="_blank">Social deprivation and SARS-CoV-2 testing: a population-based analysis in a highly contrasted Southern France region</a>
</div></li>
<li><strong>Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir among COVID-19 community, highly vaccinated patients with high risk for severe disease: Evidence that both antivirals reduce the risk for disease progression and death</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Besides the significant benefits of vaccination against COVID-19, the risk of severe disease and death from COVID-19 among highly vulnerable populations remains of concern. Implementation of oral antiviral treatment has shown significant benefits for outpatients with high risk for severe disease, however, their effectiveness remains to be evaluated in real-life settings and in the presence of new Omicron subvariants. We aimed to investigate the effectiveness of molnupiravir and nirmatrelvir/ritonavir using a retrospective cohort design with outcomes hospital admission and death from COVID-19, in Greece. The effectiveness of each drug was estimated through a comparison of the antiviral9s recipients with an age-matched control group of non-recipients, adjusted for age, previous SARS-CoV-2 infection, vaccination status, and vaccination recency. Our analysis showed that molnupiravir significantly reduced the risk for hospitalization (OR = 0.40, p &lt; 0.001) and death from COVID-19 (OR = 0.31, p &lt; 0.001), with the effect being more intense among elderly patients (&gt;=75 years old). The effectiveness was higher among those with full adherence. Nirmatrelvir/ritonavir was found also to significantly reduce the risk of hospital admission (OR = 0.31, p &lt; 0.001) and death (OR = 0.28, p &lt; 0.001) and, similarly to molnupiravir, effectiveness was stronger among elderly patients and those with the highest levels of adherence. Analysis of the relative effectiveness of nirmatrelvir/ritonavir versus molnupiravir suggested that nirmatrelvir/ritonavir was associated with a reduced risk for hospital admission (OR = 0.58, p &lt; 0.001) compared to molnupiravir, adjusted for age, previous SARS-CoV-2 infection, vaccination status, and co-morbidities. Our real-world study provides evidence about the reduced risk of hospitalization and death in highly vaccinated patients with a high risk for severe disease in Greece. These findings highlight that although the hospitalization and mortality risk has been reduced mainly due to vaccination and the emergence of Omicron variants, antivirals provide significant additional benefits in highly vulnerable patients and therefore their use is documented and strongly indicated.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.02.09.23285737v1" target="_blank">Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir among COVID-19 community, highly vaccinated patients with high risk for severe disease: Evidence that both antivirals reduce the risk for disease progression and death</a>
</div></li>
<li><strong>Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19</strong> -
<div>
<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
Importance: Post-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation of interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk of PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties and therefore may be postulated to be of benefit in patients with PASC, although clinical trial data are lacking. Objectives: The main objective was to evaluate whether SSRIs with agonist activity at the sigma-1 receptor lower the risk of PASC, since agonism at this receptor may serve as a mechanism by which SSRIs attenuate an inflammatory response. A secondary objective was to determine whether potential benefit could be traced to sigma-1 agonism by evaluating the risk of PASC among recipients of SSRIs that are not S1R agonists. Design: Retrospective study leveraging real-world clinical data within the National COVID Cohort Collaborative (N3C), a large centralized multi-institutional de-identified EHR database. Presumed PASC was defined based on a computable PASC phenotype trained on the U09.9 ICD-10 diagnosis code to more comprehensively identify patients likely to have the condition, since the ICD code has come into wide-spread use only recently. Setting: Population-based study at US medical centers. Participants: Adults (≥ 18 years of age) with a confirmed COVID-19 diagnosis date between October 1, 2021 and April 7, 2022 and at least one follow up visit 45 days post-diagnosis. Of the 17 933 patients identified, 2021 were exposed at baseline to a S1R agonist SSRI, 1328 to a non-S1R agonist SSRI, and 14 584 to neither. Exposures: Exposure at baseline (at or prior to COVID-19 diagnosis) to an SSRI with documented or presumed agonist activity at the S1R (fluvoxamine, fluoxetine, escitalopram, or citalopram), an SSRI without agonist activity at S1R (sertraline, an antagonist, or paroxetine, which does not appreciably bind to the S1R), or none of these agents. Main Outcome and Measurement: Development of PASC based on a previously validated XGBoost-trained algorithm. Using inverse probability weighting and Poisson regression, relative risk (RR) of PASC was assessed. Results: A 26% reduction in the RR of PASC (0.74 [95% CI, 0.63-0.88]; P = 5 x 10-4) was seen among patients who received an S1R agonist SSRI compared to SSRI unexposed patients and a 25% reduction in the RR of PASC was seen among those receiving an SSRI without S1R agonist activity (0.75 [95% CI, 0.62 - 0.90]; P = 0.003) compared to SSRI unexposed patients. Conclusions and Relevance: SSRIs with and without reported agonist activity at the S1R were associated with a significant decrease in the risk of PASC. Future prospective studies are warranted.
</p>
</div>
<div class="article-link article-html-link">
🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.11.09.22282142v3" target="_blank">Assessing the Effect of Selective Serotonin Reuptake Inhibitors in the Prevention of Post-Acute Sequelae of COVID-19</a>
</div></li>
</ul>
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>MG Granules Improve COVID-19 Efficacy and Safety of Convalescent Exercise Tolerance</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Manzi Guben granules<br/><b>Sponsors</b>:   Second Affiliated Hospital, School of Medicine, Zhejiang University;   The First Affiliated Hospital of Zhejiang Chinese Medical University;   Hangzhou Hospital of Traditional Chinese Medicine;   Suzhou Hospital of Traditional Chinese Medicine<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase Clinical Trial of a Candidate COVID-19 Vaccine</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Biological: Recombinant COVID-19 Vaccine (chimpanzee adenovirus vector) for Inhalation<br/><b>Sponsors</b>:   Wuhan BravoVax Co., Ltd.;   National University Hospital, Singapore;   Shanghai BravoBio Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: Plitidepsin<br/><b>Sponsor</b>:   PharmaMar<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Improving Adherence to COVID-19 Prevention Behaviours: Test of Persuasive Messages</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Behavioral: Persuasive Appeal<br/><b>Sponsor</b>:   University of Calgary<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Incidence of COVID-19 Following Vaccination in Botswana Against SARS CoV 2</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Drug: AZD 1222<br/><b>Sponsors</b>:   Botswana Harvard AIDS Institute Partnership;   AstraZeneca;   Botswana Ministry of Health<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study Evaluating GS-5245 in Nonhospitalized Participants With COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: GS-5245;   Drug: GS-5245 Placebo<br/><b>Sponsor</b>:   Gilead Sciences<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study To Assess The Efficacy and Safety of HH-120 Nasal Spray for the Treatment of Mild COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: HH-120 nasal spray;   Drug: Placebo Comparator<br/><b>Sponsor</b>:   Huahui Health<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study for Efficacy and Safety Assessment of the Drug RADAMIN®VIRO for COVID-19 Postexposure Prophylaxis</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: Double-Stranded RNA sodium salt;   Drug: Placebo<br/><b>Sponsor</b>:   Promomed, LLC<br/><b>Completed</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: VV116+SOC;   Drug: SOC<br/><b>Sponsor</b>:   Chengdu Zenitar Biomedical Technology Co., Ltd<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Access the Efficacy and Safety of STI-1558 in Adult Subjects With Mild or Moderate (COVID-19)</strong> - <b>Condition</b>:   COVID-19<br/><b>Interventions</b>:   Drug: STI-1558;   Drug: STI-1558 placebo<br/><b>Sponsor</b>:   Zhejiang ACEA Pharmaceutical Co. Ltd.<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effects of Pilates in Patients With Post- -COVID-19 Syndrome: Controlled and Randomized Clinical Trial</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Procedure: Pilates Exercises<br/><b>Sponsor</b>:   Michele de Aguiar Zacaria<br/><b>Recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pirfenidone in Adult Hospitalized Patients With COVID-19</strong> - <b>Condition</b>:   COVID-19 Pneumonia<br/><b>Interventions</b>:   Drug: Pirfenidone Oral Product;   Drug: Pirfenidone placebo<br/><b>Sponsor</b>:   Capital Medical University<br/><b>Active, not recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cells in the Treatment of Long COVID-19</strong> - <b>Condition</b>:   Long COVID-19<br/><b>Intervention</b>:   Biological: UC-MSCs<br/><b>Sponsor</b>:   Shanghai East Hospital<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INFLUENCE OF HIGH FREQUENCY CHEST WALL OSCILLATION IN HOSPITALIZED PATIENTS WITH COVID-19</strong> - <b>Condition</b>:   COVID-19<br/><b>Intervention</b>:   Device: HIGH FREQUENCY CHEST WALL OSCILLATION<br/><b>Sponsor</b>:   Cairo University<br/><b>Not yet recruiting</b></p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>CONFIDENCE: A Pilot Randomized Control Trial With Waitlist Condition to Test a Multicomponent Clinic-based Intervention to Promote COVID-19 Vaccine Intention and Uptake Among Diverse Youth and Adolescents</strong> - <b>Condition</b>:   COVID-19 Vaccination<br/><b>Intervention</b>:   Behavioral: CONFIDENCE<br/><b>Sponsors</b>:   University of Massachusetts, Worcester;   Merck Sharp &amp; Dohme LLC;   Baystate Health<br/><b>Not yet recruiting</b></p></li>
</ul>
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
<ul>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparison study of Beninese and Chinese herbal medicines in treating COVID-19</strong> - CONCLUSIONS: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The influence of facemasks on communication in healthcare settings: a systematic review</strong> - CONCLUSIONS: Despite considerable complexity and heterogeneity in outcome measure, 93% (14 of 15) articles suggest respiratory protective equipment negatively affects speech understanding in normal hearing and hearing-impaired adults.</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibitory Activity of <em>Saussurea costus</em> Extract against Bacteria, Candida, Herpes, and SARS-CoV-2</strong> - Medicinal herbs have long been utilized to treat various diseases or to relieve the symptoms of some ailments for extended periods. The present investigation demonstrates the phytochemical profile, molecular docking, anti-Candida activity, and anti-viral activity of the Saussurea costus acetic acid extract. GC-MS analysis of the extract revealed the presence of 69 chemical compounds. The chemical compounds were alkaloids (4%), terpenoids (79%), phenolic compounds (4%), hydrocarbons (7%), and…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors</strong> - The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2. Herein, we report the synthesis and study…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong><em>N</em>-Containing α-Mangostin Analogs via Smiles Rearrangement as the Promising Cytotoxic, Antitrypanosomal, and SARS-CoV-2 Main Protease Inhibitory Agents</strong> - New N-containing xanthone analogs of α-mangostin were synthesized via one-pot Smiles rearrangement. Using cesium carbonate in the presence of 2-chloroacetamide and catalytic potassium iodide, α-mangostin (1) was subsequently transformed in three steps to provide ether 2, amide 3, and amine 4 in good yields at an optimum ratio of 1:3:3, respectively. The evaluation of the biological activities of α-mangostin and analogs 2-4 was described. Amine 4 showed promising cytotoxicity against the…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells</strong> - Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety of wild Puer tea plants were two major ingredients responsible for the anti-influenza activity. As the COVID-19 outbreak is still lurking, developing safe and cost-effective therapeutics is an urgent need. This study aimed to evaluate the effects of these tea compounds on the infection of mouse hepatitis virus (MHV), a β-coronavirus serving as a surrogate for SARS-CoV. Treatment with strictinin (100 μM), but not…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Coronavirus Inhibitors Targeting nsp16</strong> - During the past three decades, humans have been confronted with different new coronavirus outbreaks. Since the end of the year 2019, COVID-19 threatens the world as a rapidly spreading infectious disease. For this work, we targeted the non-structural protein 16 (nsp16) as a key protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV to develop broad-spectrum inhibitors of nsp16. Computational methods were used to filter candidates from a natural product-based library of 224,205 compounds obtained from…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Quercetin: A Functional Food-Flavonoid Incredibly Attenuates Emerging and Re-Emerging Viral Infections through Immunomodulatory Actions</strong> - Many of the medicinally active molecules in the flavonoid class of phytochemicals are being researched for their potential antiviral activity against various DNA and RNA viruses. Quercetin is a flavonoid that can be found in a variety of foods, including fruits and vegetables. It has been reported to be effective against a variety of viruses. This review, therefore, deciphered the mechanistic of how Quercetin works against some of the deadliest viruses, such as influenza A, Hepatitis C, Dengue…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Silico and In Vitro Inhibition of SARS-CoV-2 PL<sup>pro</sup> with Gramicidin D</strong> - Finding an effective drug to prevent or treat COVID-19 is of utmost importance in tcurrent pandemic. Since developing a new treatment takes a significant amount of time, drug repurposing can be an effective option for achieving a rapid response. This study used a combined in silico virtual screening protocol for candidate SARS-CoV-2 PL^(pro) inhibitors. The Drugbank database was searched first, using the Informational Spectrum Method for Small Molecules, followed by molecular docking. Gramicidin…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Links between COVID-19 and Alzheimers Disease-What Do We Already Know?</strong> - Alzheimers disease (AD) is a life-changing condition whose etiology is explained by several hypotheses. Recently, a new virus contributed to the evidence of viral involvement in AD: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the COVID-19 coronavirus disease. AD was found to be one of the most common COVID-19 comorbidities, and it was found to increase mortality from this disease as well. Moreover, AD patients were observed to present with the distinct…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Formalin Inactivation of Virus for Safe Downstream Processing of Routine Stool Parasite Examination during the COVID-19 Pandemic</strong> - During the COVID-19 pandemic, the parasitology laboratories dealing with fecal samples for the diagnosis of gastrointestinal parasitic infections are confronting the unsaved virus-containing samples. To allow for safe downstream processing of the fecal samples, a protocol for preparing a fecal smear is urgently needed. Formalin was tested with or without isotonic forms for virus inactivation using porcine epidemic diarrhea virus (PEDV) as a representative, as it belongs to the Coronaviridae…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Metagenomic insights into the effects of benzyl dodecyl dimethyl ammonium bromide (BDAB) shock on bacteria-driven nitrogen removal in a moving-bed biofilm reactor (MBBR)</strong> - The use of disinfectants made from quaternary ammonium compounds (QACs) has greatly increased since the outbreak of SARS-CoV-2. However, the effect of QACs on wastewater treatment performance is still unclear. In this study, a commonly used QAC, i.e., benzyl dodecyl dimethyl ammonium bromide (BDAB), was added to a moving-bed biofilm reactor (MBBR) to investigate BDABs effect on nutrient removal. When the BDAB concentration was increased to 50 mg L^(-1), the ammonia removal efficiency (ARE)…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SS148 and WZ16 inhibit the activities of nsp10-nsp16 complexes from all seven human pathogenic coronaviruses</strong> - Seven coronaviruses have infected humans (HCoVs) to-date. SARS-CoV-2 caused the current COVID-19 pandemic with the well-known high mortality and severe socioeconomic consequences. MERS-CoV and SARS-CoV caused epidemic of MERS and SARS, respectively, with severe respiratory symptoms and significant fatality. However, HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43 cause respiratory illnesses with less severe symptoms in most cases. All coronaviruses use RNA capping to evade the immune systems of…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum α-Glucosidase I with Anti-SARS-CoV-2 Activity</strong> - Enveloped viruses depend on the host endoplasmic reticulum (ER) quality control (QC) machinery for proper glycoprotein folding. The endoplasmic reticulum quality control (ERQC) enzyme α-glucosidase I (α-GluI) is an attractive target for developing broad-spectrum antivirals. We synthesized 28 inhibitors designed to interact with all four subsites of the α-GluI active site. These inhibitors are derivatives of the iminosugars 1-deoxynojirimycin (1-DNJ) and valiolamine. Crystal structures of ER…</p></li>
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Computational investigation on the antioxidant activities and on the M<sup>pro</sup> SARS-CoV-2 non-covalent inhibition of isorhamnetin</strong> - In the present work, we report a computational study on some important chemical properties of the flavonoid isorhamnetin, used in traditional medicine in many countries. In the course of the study we determined the acid-base equilibria in aqueous solution, the possible reaction pathways with the •OOH radical and the corresponding kinetic constants, the complexing capacity of copper ions, and the reduction of these complexes by reducing agents such as superoxide and ascorbic anion by using…</p></li>
</ul>
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
<script>AOS.init();</script></body></html>