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<title>05 March, 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>When police pull back: Neighborhood-level effects of de-policing on violent and property crime</strong> -
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<div>
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Many U.S. cities witnessed both de-policing and increased crime in 2020, yet it remains unclear whether the former contributed to the latter. Indeed, much of what is known about the effects of proactive policing on crime comes from studies that evaluate highly focused interventions atypical of day-to-day policing, use cities as the unit of analysis, or cannot rule out endogeneity. This study addresses each of these issues, thereby advancing the evidence base concerning the effects of policing on crime. Leveraging two exogenous shocks presented by the onset of COVID-19 and social unrest following the murder of George Floyd, we evaluated the effects of sudden and sustained reductions in high-discretion policing on crime at the neighborhood level in Denver. Multilevel models accounting for trends in prior police activity, neighborhood structure, seasonality, and population mobility revealed mixed results. On one hand, large-scale reductions in pedestrian stops and drug-related arrests were associated with significant increases in violent and property crimes, respectively. On the other hand, fewer vehicle stops and disorder arrests did not affect crime. These results were not universal across neighborhoods. We discuss the implications of these findings in light of debates concerning the appropriate role of policing in the 21st century.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/54dyh/" target="_blank">When police pull back: Neighborhood-level effects of de-policing on violent and property crime</a>
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</div></li>
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<li><strong>Scalable neighbour search and alignment with uvaia</strong> -
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<div>
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Despite millions of SARS-CoV-2 genomes being sequenced and shared globally, manipulating such data sets is still challenging, especially selecting sequences for focused phylogenetic analysis. We present a novel method, uvaia, which is based on partial and exact sequence similarity for quickly extracting database sequences similar to query sequences of interest. Many SARS-CoV-2 phylogenetic analyses rely on very low numbers of ambiguous sites as a measure of quality since ambiguous sites do not contribute to single nucleotide polymorphism (SNP) differences, which uvaia alleviates by using measures of sequence similarity that consider partially ambiguous sites. Such fine-grained definition of similarity allows not only for better phylogenetic analyses, but also for improved classification and biogeographical inferences. Uvaia works natively with compressed files, can use multiple cores and efficiently utilises memory, being able to analyse large data sets on a standard desktop.
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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/10.1101/2023.01.31.526458v2" target="_blank">Scalable neighbour search and alignment with uvaia</a>
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</div></li>
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<li><strong>Frequent emergence of resistance mutations following complex intra-host genomic dynamics in SARS-CoV-2 patients receiving Sotrovimab</strong> -
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<div>
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The emergence of the Omicron variant of SARS-CoV-2 represented a challenge to the treatment of COVID-19 with monoclonal antibodies. Only Sotrovimab maintained partial activity, allowing it to be used in high-risk patients infected with the Omicron variant. However, the reports of resistance mutations to Sotrovimab call for efforts to better understand the intra-patient emergence of this resistance. A retrospective genomic analysis was conducted on respiratory samples from immunocompromised patients infected with SARS-CoV-2 who received Sotrovimab at our hospital between December 2021 and August 2022. The study involved 95 sequential specimens from 22 patients (1-12 samples/patient; 3-107 days post-infusion (Ct [≤] 32)). Resistance mutations (in P337, E340, K356, and R346) were detected in 68% of cases; the shortest time to detection of a resistance mutation was 5 days after Sotrovimab infusion. The dynamics of resistance acquisition were highly complex, with up to 11 distinct amino acid changes in specimens from the same patient. In two patients, the mutation distribution was compartmentalized in respiratory samples from different sources. This is the first study to examine the acquisition of resistance to Sotrovimab in the BA.5 lineage, enabling us to determine the lack of genomic or clinical differences between Sotrovimab resistance in BA.5 relative to BA.1/2. Across all Omicron lineages, the acquisition of resistance delayed SARS-CoV-2 clearance (40.67 vs 19.5 days). Close, real-time genomic surveillance of patients receiving Sotrovimab should be mandatory to facilitate early therapeutic interventions.
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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/10.1101/2023.03.01.530733v1" target="_blank">Frequent emergence of resistance mutations following complex intra-host genomic dynamics in SARS-CoV-2 patients receiving Sotrovimab</a>
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</div></li>
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<li><strong>Residual Sanitization of Three Human Respiratory Viruses on a Hard, Non-Porous Surface</strong> -
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<div>
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Human pathogenic viruses that are present in bioaerosols released by coughing, sneezing, or breathing can contaminate fomites and other inanimate environmental surfaces. Most are enveloped respiratory viruses that are vulnerable to inactivation by a broad spectrum of antimicrobial actives. Quaternary ammonium compounds are highly diverse in structure and are among the most widely utilized antimicrobial agents. The objective of this study was to evaluate two commercially available, ready-to-use quaternary ammonium compound-based disinfectants (one of which also contains a surface binding agent) for antiviral activity against Influenza A (H1N1), human coronavirus 229E, and SARS-CoV-2 (Washington) following a rigorous procedure of wear and abrasions with regular re-inoculations of virus in the presence of a 6% organic soil load. Formulation TF-A demonstrated variable residual efficacy against the three viruses, achieving log10 reductions of 1.62, 3.33, and 0.92, respectively. Formulation TF-B lowered each test virus by greater than 3-log10 to non-detectable levels on all carriers in demonstration of residual antiviral activity.
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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/10.1101/2023.03.02.530883v1" target="_blank">Residual Sanitization of Three Human Respiratory Viruses on a Hard, Non-Porous Surface</a>
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</div></li>
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<li><strong>The infectivity of SARS-CoV-2 progeny virions requires the activity of host cell N-myristoyltransferases and it is severely compromised by their inhibition</strong> -
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<div>
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Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Despite vaccinations, the development and use of neutralising antibodies against the viral surface spike proteins, and small molecule inhibitors targeting the viral replication machinery, COVID-19 remains a global public health crisis. Emerging mutations in the viral genome have the potential to reduce prophylactic and therapeutic efficacy of virus-directed treatments. Targeting host cell factors required for infection could, therefore, be a potential strategy to overcome this problem since mutations in the viral genome are unlikely to bypass the requirement for the targeted host factor or function. The enzymatic activity of N-myristoyltransferases (NMTs) are essential to mediate stable membrane binding and function of a diverse class of cellular proteins, many of which regulate intracellular membrane trafficking. Here we report that nanomolar concentrations of the NMT inhibitor IMP-1088 inhibited SARS-CoV-2 spreading in human cells by compromising the infectivity of released viral particles, which was reduced by up to 90%. IMP-1088 also inhibited human Respiratory syncytial virus, the main cause of viral death in infants world-wide, but not the mosquito-delivered alphavirus Semliki Forest virus and the vesiculovirus Vesicular stomatitis virus. The antiviral effect of IMP-1088 against SARS-CoV-2 displayed remarkably slow reversibility, was well tolerated by cells, and is, therefore, a promising candidate for COVID-19 prophylaxis and therapy.
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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/10.1101/2023.03.03.530798v1" target="_blank">The infectivity of SARS-CoV-2 progeny virions requires the activity of host cell N-myristoyltransferases and it is severely compromised by their inhibition</a>
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</div></li>
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<li><strong>SARS-CoV-2 post-vaccine surveillance studies in Australian children and adults with cancer: SerOzNET Quality of Life, Toxicity and Vaccine Beliefs Substudy Statistical Analysis Plan</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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COVID-19 disease is associated with higher morbidity and mortality in cancer patients. SerOzNET is a prospective cohort study of adults and children with cancer undergoing routine SARS-CoV-2 vaccination in Australia. Peripheral blood was collected and processed at multiple points (one pre-vaccination and five or more post-vaccination) to address the primary aim of the study to assess the serological and immunological responses to vaccination. A secondary aim of the study was to document patient response to vaccination using qualitative measures, including patient-reported outcomes, vaccine hesitancy survey and post-hoc toxicity recording (body, et al.,2022). This statistical analysis plan describes the analysis of the data collected to address this aim. We will refer to this as the SerOzNET QoL Substudy.
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</p>
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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.medrxiv.org/content/10.1101/2023.02.28.23286595v1" target="_blank">SARS-CoV-2 post-vaccine surveillance studies in Australian children and adults with cancer: SerOzNET Quality of Life, Toxicity and Vaccine Beliefs Substudy Statistical Analysis Plan</a>
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</div></li>
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<li><strong>Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of Long-Term Care Facilities in the VIVALDI study</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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We evaluated the effectiveness of 1-3 booster vaccinations against SARS-CoV-2 related mortality among a cohort of 13407 older residents of long-term care facilities (LTCFs) participating in the VIVALDI study in England in 2022. Cox regression was used to estimate relative hazards of SARS-CoV-2 related death following booster vaccination relative to 2 doses (after 84+ days), stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF capacity. Each booster provided additional short-term protection relative to primary vaccination, with consistent pattern of waning to 45-75% reduction in risk beyond 112 days.
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</p>
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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.medrxiv.org/content/10.1101/2023.03.01.23286627v1" target="_blank">Effectiveness of successive booster vaccine doses against SARS-CoV-2 related mortality in residents of Long-Term Care Facilities in the VIVALDI study</a>
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</div></li>
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<li><strong>Virological evidence of the impact of non-pharmaceutical interventions against COVID-19 in a resource-limited setting</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Ecuador was an early COVID-19 hotspot with substantial COVID-19-mortality. In developed countries, low socioeconomic status is associated with COVID-19 infection and low compliance with non-pharmaceutical interventions (NPIs). However, if NPI were successful in resource-limited settings with high human mobility and informal labour is still unclear. We performed a retrospective observational molecular and serological study of Ecuadors reference laboratory. We tested 1,950 respiratory samples from COVID-19 surveillance for SARS-CoV-2 and 12 respiratory viruses using RT-PCR, characterized 642 SARS-CoV-2 genomes, and examined SARS-CoV-2 seroprevalence in 1,967 samples from patients with fever in Ecuadors reference laboratory during 2020-2021. Molecular and serological data were compared to NPI stringency in Bayesian, maximum-likelihood and modelling frameworks. SARS-CoV-2 (Pearson correlation test; r=-0.74; p=0.01) and other respiratory viruses (r=-0.68; p=0.02) detection correlated negatively with NPI stringency. SARS-CoV-2 seroprevalence increased from <1% during February-March 2020 to 50% within 6 weeks and plateaued after NPI implementation. Decrease of effective reproduction number <1 and antibody reactivity over time suggested intense SARS-CoV-2 transmission during pandemic onset, subsequently limited by NPIs. Phylogeographic analyses revealed that travel restrictions were implemented late not preventing 100 near-parallel SARS-CoV-2 introductions, and implementation of NPIs modified SARS-CoV-2 geographic spread by restricting recreational activity. NPIs stringency correlated negatively with the number of circulating SARS-CoV-2 lineages (r=-0.69; p=0.02). Virological evidence supports NPIs restricting human movement as an effective public health tool to control the spread of respiratory pathogens in resource-limited settings, providing a template for emerging SARS-CoV-2 variants and future epidemics.
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</p>
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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.medrxiv.org/content/10.1101/2023.03.01.23286616v1" target="_blank">Virological evidence of the impact of non-pharmaceutical interventions against COVID-19 in a resource-limited setting</a>
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</div></li>
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<li><strong>Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease</strong> -
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<div>
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background COVID-19 is associated with a higher risk of cardiovascular outcomes in the general population. People with chronic respiratory disease have a higher risk of cardiovascular disease than the general population therefore, we investigated the association between pre-existing chronic respiratory disease and risk of cardiovascular events following COVID-19 using routinely collected data from 56 million people in England. Methods Primary and secondary care data from the English National Health Service and COVID-19-specific linked data were used to define a population of adults with COVID-19 between 01/01/2020-30/11/2021. Start of follow-up was from first COVID-19 diagnosis. Pre-existing chronic respiratory disease included asthma, chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, or pulmonary fibrosis prior to COVID-19 diagnosis. Adjusted Cox Proportional Hazard regression was used to investigate the association between pre-existing chronic respiratory disease and risk of cardiovascular events. Secondary objectives investigated the impact of COVID-19 hospitalisation and vaccine dose on risk of cardiovascular outcomes. Findings A total of 3,670,455 people were included. People with pre-existing respiratory disease had a higher risk of cardiovascular events (adjusted HR 1.11, 95% confidence intervals 1.07-1.14), heart failure (1.15, 1.09-1.21), and pulmonary embolism (1.20, 1.11-1.30) compared with those without pre-existing respiratory disease. Regardless of pre-existing respiratory disease, the risk of cardiovascular events was lower with increasing COVID-19 vaccine dose. Interpretation People with chronic respiratory disease have a higher risk of some cardiovascular outcomes but the risk might be explained by the underlying respiratory condition. Risk of cardiovascular events was lower with increasing COVID-19 vaccine doses regardless of pre-existing chronic respiratory disease. Funding This work was funded by the British Heart Foundation Data Science Centre.
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</p>
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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.medrxiv.org/content/10.1101/2023.03.01.23286624v1" target="_blank">Risk of cardiovascular events following COVID-19 in people with and without pre-existing chronic respiratory disease</a>
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</div></li>
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<li><strong>MANAGEMENT OF RISK FACTORS FOR HEALTH CARE WORKERS AFTER INITIAL CONTACT WITH PATIENTS INFECTED WITH SARS-CoV-2 IN NIAMEY, THE CENTER OF THE EPIDEMIC IN NIGER</strong> -
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<p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom">
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Background: The covid-19 pandemic is caused by a new corona virus called SARS Cov-2. Health care workers are particularly exposed target. Aim: this study aims to analyze the risk factors of SARS-Cov-2 infection in health workers who have been in contact with positive patient. Methods: This is a prospective cohort conducted among health workers from March 2022 to January 2021 in health care facilities in Niamey. A questionnaire was administrated at inclusion. rRT-PCR was performed if clinical signs were present. ELISA testing was performed at baseline, day15 and day 30. The chi-square or Fisher test, Kaplan-Meir survival model, Cow regression and logistic regression were used as statistical test. Results: 259 health workers were included. More than half of the respondents were female. 45.95% of the participants were nurses and 36.68% were physicians. The prevalence of Covid-19 was 28.8%. 56.4% of the participants had positive serology at day 30. The risk factors associated with Covid-19 were professional category (p=0.024). Membership structure (p<0.001) and the chronic liver disease (p=0.034). Hand hygiene (p=0.019) and alcohol-based hand cleaning (p<0.001) protects against the occurrence of SARS-Cov-2 infection. According to the characterization of the preventive measures those who practiced them rarely were associated with a positive rRT-PCR and those who practice them occasionally or most of the time were associated with negative serology and rRT-PCR. Conclusion: Comorbidities, function and affiliation are the main risk factors for Covid-19 and hand hygiene is a protective factor.
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</p>
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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.medrxiv.org/content/10.1101/2023.03.01.23286420v1" target="_blank">MANAGEMENT OF RISK FACTORS FOR HEALTH CARE WORKERS AFTER INITIAL CONTACT WITH PATIENTS INFECTED WITH SARS-CoV-2 IN NIAMEY, THE CENTER OF THE EPIDEMIC IN NIGER</a>
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</div></li>
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<li><strong>Warning “Don’t spread” vs. “Don’t be a spreader” to prevent the COVID-19 pandemic</strong> -
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<div>
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The coronavirus disease 2019 (COVID-19) outbreak is threatening not only health but also life worldwide. It is important to encourage citizens to voluntarily practise infection prevention (IP) behaviours such as social distancing and self-restraint. Previous research on social cognition suggested that emphasising self-identity is key to changing a person’s behaviour. The present study investigated whether reminders that highlight self-identity would be effective in changing intention and behaviour related to the COVID-19 outbreak, and hypothesised that those who read reminders highlighting self-identity (‘Don’t be a spreader’) would change IP intention and behaviour better than those who read ‘Don’t spread’ or no reminder. We conducted a two-wave survey of the same participants with a one-week interval, during which we assigned one of three reminder conditions to the participants: ‘Don’t spread’ (spreading condition), ‘Don’t be a spreader’ (spreader condition), and no reminder (control condition). Participants marked their responses to IP intentions and actual behaviours each week based on the Japanese Ministry of Health, Labour, and Welfare guidelines. While the results did not show significant differences between the conditions, the post-hoc analyses showed significant equivalence in either IP intentions or behavioural scores. We discussed the results from the perspective of the effect size, ceiling effects, and ways of manipulation checks as future methods with more effective persuasive messaging. Following in-principle acceptance, the approved Stage 1 version of this manuscript was preregistered on the OSF at https://doi.org/10.17605/OSF.IO/KZ5Y4. This preregistration was performed prior to data collection and analysis.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/u4z3e/" target="_blank">Warning “Don’t spread” vs. “Don’t be a spreader” to prevent the COVID-19 pandemic</a>
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</div></li>
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<li><strong>Distancing from a stigmatized identity: Explaining hostility by marginalized racial groups toward new immigrants</strong> -
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<div>
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Discrimination is often perceived as stemming from outgroups. The UN Sustainable Development Goal 10 focused on reducing inequalities calls attention also to intragroup hostilities. In the US, intragroup hostilities between Latinos/as might occur if disassociation from a stigmatized sub-group protects one’s status. This chapter tests potential disassociation effects by examining whether US Latinos/as distance themselves from an associated stigmatized identity by supporting adverse policies regarding Latino/a immigrants. Two studies (n=273 and n=8634) found that citizenship status was linked to support for adverse policies: more US-born Latinos/as considered immigrants a burden than Latinos/as of unknown status or non-citizens. Some Latino/a citizens might cut off reflected failure associated with being an immigrant because distancing might support coping with cultural demands of US residence and distancing from recent immigrants might prevent transference of negative stereotypes. As inequalities increase overall in the post-COVID-19 era, intragroup bias may worsen outcomes for stigmatized sub-groups.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://psyarxiv.com/za8u9/" target="_blank">Distancing from a stigmatized identity: Explaining hostility by marginalized racial groups toward new immigrants</a>
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</div></li>
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<li><strong>Systematic analyses of the resistance potential of drugs targeting SARS-CoV-2 main protease</strong> -
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<div>
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Drugs that target the main protease (Mpro) of SARS-CoV-2 are effective therapeutics that have entered clinical use. Wide-scale use of these drugs will apply selection pressure for the evolution of resistance mutations. To understand resistance potential in Mpro, we performed comprehensive surveys of amino acid changes that can cause resistance in a yeast screen to nirmatrelvir (contained in the drug Paxlovid), and ensitrelvir (Xocova) that is currently in phase III trials. The most impactful resistance mutation (E166V) recently reported in multiple viral passaging studies with nirmatrelvir showed the strongest drug resistance score for nirmatrelvir, while P168R had the strongest resistance score for ensitrelvir. Using a systematic approach to assess potential drug resistance, we identified 142 resistance mutations for nirmatrelvir and 177 for ensitrelvir. Among these mutations, 99 caused apparent resistance to both inhibitors, suggesting a strong likelihood for the evolution of cross-resistance. Many mutations that exhibited inhibitor-specific resistance were consistent with distinct ways that each inhibitor protrudes beyond the substrate envelope. In addition, mutations with strong drug resistance scores tended to have reduced function. Our results indicate that strong pressure from nirmatrelvir or ensitrelvir will select for multiple distinct resistant lineages that will include both primary resistance mutations that weaken interactions with drug while decreasing enzyme function and secondary mutations that increase enzyme activity. The comprehensive identification of resistance mutations enables the design of inhibitors with reduced potential of developing resistance and aids in the surveillance of drug resistance in circulating viral populations.
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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/10.1101/2023.03.02.530652v1" target="_blank">Systematic analyses of the resistance potential of drugs targeting SARS-CoV-2 main protease</a>
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</div></li>
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<li><strong>Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping</strong> -
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<div>
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The emergence of new variants of the SARS-CoV-2 virus has posed a significant challenge in developing broadly neutralizing antibodies (nAbs) with guaranteed therapeutic potential. Some nAbs, such as Sotrovimab, have exhibited varying levels of efficacy against different variants, while others, such as Bebtelovimab and Bamlanivimab-etesevimab are ineffective against specific variants, including BQ.1.1 and XBB. This highlights the urgent need for developing broadly active mAbs providing prophylactic and therapeutic benefits to high-risk patients, especially in the face of the risk of reinfection from new variants. Here, we aimed to investigate the feasibility of redirecting existing mAbs against new variants of SARS-CoV-2, as well as to understand how BQ.1.1 and XBB.1.5 can evade broadly neutralizing mAbs. By mapping epitopes and escape sites, we discovered that the new variants evade multiple mAbs, including FDA-approved Bebtelovimab, which showed resilience against other Omicron variants. Our approach, which included simulations, free energy perturbations, and shape complementarity analysis, revealed the possibility of identifying mAbs that are effective against both BQ.1.1 and XBB.1.5. We identified two broad-spectrum mAbs, R200-1F9 and R207-2F11, as potential candidates with increased binding affinity to XBB.1.5 and BQ.1.1 compared to the wild-type virus. Additionally, we propose that these mAbs do not interfere with ACE2 and bind to conserved epitopes on the RBD that are not-overlapping, potentially providing a solution to neutralize these new variants either independently or as part of a combination (cocktail) treatment.
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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/10.1101/2023.03.01.530717v1" target="_blank">Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping</a>
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</div></li>
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<li><strong>Isolation of ACE2-dependent and -independent sarbecoviruses from Chinese horseshoe bats</strong> -
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<div>
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While the spike proteins from SARS-CoV and SARS-CoV-2 bind to host ACE2 to infect cells, the majority of bat sarbecoviruses cannot use ACE2 from any species. Despite their discovery almost 20 years ago, ACE2-independent sarbecoviruses have never been isolated from field samples, leading to the assumption these viruses pose little risk to humans. We have previously shown how spike proteins from a small group of ACE2-independent bat sarbecoviruses may possess the ability to infect human cells in the presence of exogenous trypsin. Here, we adapted our earlier findings into a virus isolation protocol, and recovered two new ACE2-dependent viruses, RsYN2012 and RsYN2016, as well as an ACE2-independent virus, RsHuB2019. Although our stocks of RsHuB2019 rapidly acquired a tissue-culture adaption that rendered the spike protein resistant to trypsin, trypsin was still required for viral entry, suggesting limitations on the exogenous entry factors that support bat sarbecoviruses. Electron microscopy revealed ACE2-independent sarbecoviruses have a prominent spike corona and share similar morphology to other coronaviruses. Our findings demonstrate a broader zoonotic threat posed by sarbecoviruses and shed light onto the intricacies of coronavirus isolation and propagation in vitro.
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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/10.1101/2023.03.02.530738v1" target="_blank">Isolation of ACE2-dependent and -independent sarbecoviruses from Chinese horseshoe bats</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>Exercise Training Six-Months After Discharge in Post-COVID-19 Syndrome</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Intervention</b>: Other: Aerobic exercise and strength training<br/><b>Sponsor</b>: Ukbe Sirayder<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm C (Fluticasone)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Fluticasone; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACTIV-6: COVID-19 Study of Repurposed Medications - Arm A (Ivmermectin 400)</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Drug: Ivermectin; Other: Placebo<br/><b>Sponsors</b>: Susanna Naggie, MD; National Center for Advancing Translational Sciences (NCATS); Vanderbilt University Medical Center<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Counter-Regulatory Hormonal and Stress Systems in Patients With COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: Blood sampling<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploratory Efficacy of N-Acetylcysteine in Patients With History of COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: N-Acetylcysteine; Drug: Placebo<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Effect of Selected Types of Breathing Exercises on Different Outcome Measures in Covid-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Other: breathing exercise<br/><b>Sponsor</b>: Basma Mosaad Abd-elrahman Abushady<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Specific miRNA Encoded by SARS-CoV-2 as a Diagnostic Tool to Predict Disease Severity in COVID-19 Patients</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Diagnostic Test: miRNA analysis in plasma<br/><b>Sponsor</b>: Fondazione Policlinico Universitario Agostino Gemelli IRCCS<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Telerehabilitation in the Post-COVID-19 Patient (TRIALS)</strong> - <b>Condition</b>: Post-COVID-19 Syndrome<br/><b>Intervention</b>: Other: Telerehabilitation program<br/><b>Sponsor</b>: Istituto Auxologico Italiano<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Application and Research of Mesenchymal Stem Cells in Alleviating Severe Development of COVID-19 Infection</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Umbilical cord mesenchymal stem cells implantation; Other: Comparator<br/><b>Sponsor</b>: Hebei Medical University<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Reactogenicity of the 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>Conditions</b>: Vaccine Reaction; COVID-19<br/><b>Interventions</b>: Biological: Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech); Biological: VidPrevtyn® Beta vaccine (Sanofi/GSK)<br/><b>Sponsors</b>: Assistance Publique - Hôpitaux de Paris; IREIVAC/COVIREIVAC Network<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study of WPV01 Compared With Placebo in Patients With Mild/Moderate COVID-19 Infection</strong> - <b>Condition</b>: COVID-19 Infection<br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo<br/><b>Sponsor</b>: Westlake Pharmaceuticals (Hangzhou) 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>ARVAC-A New Recombinant Coronavirus Disease 2019 (COVID-19)</strong> - <b>Condition</b>: COVID-19 Vaccine<br/><b>Interventions</b>: Biological: Gamma Variant RBD-based ARVAC-CG vaccine; Biological: Omicron Variant RBD-based ARVAC-CG vaccine; Biological: Bivalent RBD-based ARVAC-CG vaccine; Other: Placebo<br/><b>Sponsors</b>: Mónica Edith Lombardo; Universidad Nacional de San Martín (UNSAM); National Council of Scientific and Technical Research, Argentina; Laboratorio Pablo Cassará S.R.L.<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>A Study of HH-120 Nasal Spray in Close Contacts of Those Diagnosed With COVID-19</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Intervention</b>: Drug: HH-120 Nasal Spray<br/><b>Sponsor</b>: Beijing Ditan Hospital<br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Mitigating Mental and Social Health Outcomes of COVID-19: A Counseling Approach</strong> - <b>Conditions</b>: Social Determinants of Health; Mental Health Issue; COVID-19<br/><b>Interventions</b>: Other: Individual Counseling; Other: Group Counseling; Other: Resources<br/><b>Sponsors</b>: New Mexico State University; National Institutes of Health (NIH)<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 2 Trial of the Immunogenicity and Safety of CVXGA1 Intranasal COVID Vaccine in Healthy Adults</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Biological: CVXGA1<br/><b>Sponsor</b>: CyanVac LLC<br/><b>Not yet recruiting</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Pharmacokinetics and Pharmacodynamics of Imatinib for Optimal Drug Repurposing from Cancer to COVID-19</strong> - CONCLUSION: COVID-19 patients exhibit higher total imatinib exposure compared to cancer patients, attributed to differences in plasma protein concentrations. Higher imatinib exposure in COVID-19 patients did not associate with improved clinical outcomes. Total C(trough) and AUC(ave) inversely associated with some PD-outcomes, which may be biased by disease course, variability in metabolic rate and protein binding. Therefore, additional PKPD analyses into unbound imatinib and its main metabolite…</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>Establishment of angiotensin-converting enzyme 2 and cluster of differentiation 147 dual target cell membrane chromatography based on SNAP-tag technology for screening anti severe acute respiratory syndrome coronavirus 2 active components</strong> - Patients have different responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and these may be life-threatening for critically ill patients. Screening components that act on host cell receptors, especially multi-receptor components, is challenging. The in-line combination of dual-targeted cell membrane chromatography and a liquid chromatography-mass spectroscopy (LC-MS) system for analyzing angiotensin-converting enzyme 2 (ACE2) and cluster of differentiation 147…</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>Design and characterization of novel SARS-CoV-2 fusion inhibitors with N-terminally extended HR2 peptides</strong> - Development of potent and broad-spectrum antivirals against SARS-CoV-2 remains one of top priorities, especially in the case of that current vaccines cannot effectively prevent viral transmission. We previously generated a group of fusion-inhibitory lipopeptides, with one formulation being evaluated under clinical trials. In this study, we dedicated to characterize the extended N-terminal motif (residues 1161-1168) of the so-called spike (S) heptad repeat 2 (HR2) region. Alanine scanning…</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>Pinosrtobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism</strong> - Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid…</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>Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants</strong> - Host-viral interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N6-methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during a stress response. Gene expression profiles observed post-infection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers…</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>Dual mechanism: Epigenetic inhibitor apabetalone reduces SARS-CoV-2 Delta and Omicron variant spike binding and attenuates SARS-CoV-2 RNA induced inflammation</strong> - The SARS-CoV-2 virus initiates infection via interactions between the viral spike protein and the ACE2 receptors on host cells. Variants of concern have mutations in the spike protein that enhance ACE2 binding affinity, leading to increased virulence and transmission. Viral RNAs released after entry into host cells trigger interferon-I (IFN-I) mediated inflammatory responses for viral clearance and resolution of infection. However, overreactive host IFN-I responses and pro-inflammatory signals…</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>Immune evasion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); molecular approaches</strong> - In December 2019, a new betacoronavirus, known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused an outbreak at the Wuhan seafood market in China. The disease was further named coronavirus disease 2019 (COVID-19). In March 2020, the World Health Organization (WHO) announced the disease to be a pandemic, as more cases were reported globally. SARS-CoV-2, like many other viruses, employs diverse strategies to elude the host immune response and/or counter immune responses. The…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro and in vivo suppression of SARS-CoV-2 replication by a modified, short, cell-penetrating peptide targeting the C-terminal domain of the viral spike protein</strong> - Peptides are promising therapeutic agents for COVID-19 because of their specificity, easy synthesis, and ability to be fine-tuned. We previously demonstrated that a cell-permeable peptide corresponding to the SARS-CoV-2 Spike C-terminal domain (CD) inhibits the interaction between viral spike and nucleocapsid proteins that results in SARS-CoV-2 replication in vitro. Here, we used docking studies to design R-t-Spike CD(D), a more potent short cell-penetrating peptide composed of all D-form amino…</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>Development of a screening platform to discover natural products active against SARS-CoV-2 infection using lung organoid models</strong> - CONCLUSION: This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants</strong> - SARS-CoV-2 variants have emerged with elevated transmission and a higher risk of infection for vaccinated individuals. We demonstrate that a recombinant prefusion-stabilized spike (rS) protein vaccine based on Beta/B.1.351 (rS-Beta) produces a robust anamnestic response in baboons against SARS-CoV-2 variants when given as a booster one year after immunization with NVX-CoV2373. Additionally, rS-Beta is highly immunogenic in mice and produces neutralizing antibodies against WA1/2020, Beta/B.1.351,…</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>Cyanovirin-N binds to select SARS-CoV-2 spike oligosaccharides outside of the receptor binding domain and blocks infection by SARS-CoV-2</strong> - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped positive stranded RNA virus which has caused the recent deadly pandemic called COVID-19. The SARS-CoV-2 virion is coated with a heavily glycosylated Spike glycoprotein which is responsible for attachment and entry into target cells. One, as yet unexploited strategy for preventing SARS-CoV-2 infections, is the targeting of the glycans on Spike. Lectins are carbohydrate-binding proteins produced by plants, algae, and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 infection in cellular systems using engineered trimeric receptor-binding domain of spike protein</strong> - Here, we provide a protocol for the design, expression, purification, and functional studies of an engineered trimeric version of the receptor-binding domain (tRBD) of SARS-CoV-2 spike protein. We describe the use of tRBD to block SARS-CoV-2 spike pseudovirus and true virus binding to cellular angiotensin converting enzyme-2 (ACE2), thereby blocking viral infection. This protocol is applicable to generate a trimeric version of any protein of interest. For complete details on the use and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and Biodistribution of Nanoligomers Targeting the SARS-CoV-2 Genome for the Treatment of COVID-19</strong> - As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An approach combining deep learning and molecule docking for drug discovery of cathepsin L</strong> - CONCLUSION: Our approach enables drug discovery from large-scale databases with little computational consumption, which will save the cost and time required for drug discovery.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Search of Novel Small Molecule Inhibitors for the Main Protease of SARS-CoV-2</strong> - The current outbreak of coronavirus disease 2019 (COVID-19) has prompted the necessity of efficient treatment strategies. The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Main protease (Mpro), also called 3-chymotrypsin-like protease (3CL protease), plays an essential role in cleaving virus polyproteins for the functional replication complex. Therefore, Mpro is a promising drug target for COVID-19 therapy. Through molecular modelling, docking…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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