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<title>30 April, 2022</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Machine learning in a time of COVID-19 – Can machine learning support Community Health Workers (CHWs) in low and middle income countries (LMICs) in the new normal?</strong> -
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Now, in the time of COVID-19, such measures are even more important. If the promises held out for the universal acceptability and efficacy of ML and person-centric health care are to be realised, ML must be affordable at a grassroots level in LMICs. More collaboration and co-design involving mobile health developers, mobile telecoms companies, governments, trans-national organisations and non-governmental organisations (NGOs) could result in affordable generic open-source templates. Most importantly, such a collaboration needs to be done in parallel with paying CHWs a living wage. Achieving such a goal would remove the need for any CHW ever having to resort to prostitution to purchase medicines in order to treat their patients.
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🖺 Full Text HTML: <a href="https://osf.io/eknj9/" target="_blank">Machine learning in a time of COVID-19 – Can machine learning support Community Health Workers (CHWs) in low and middle income countries (LMICs) in the new normal?</a>
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</div></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Predicting self-harm and suicide ideation during the COVID-19 pandemic in Indonesia: A nationwide survey report</strong> -
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Background: It is estimated that 77.0% of suicide cases occurred in low-and-middle-income countries (LMICs), which would increase because of the COVID-19 pandemic and socioeconomic inequity. However, there is lack of reports on this topic from LMICs, especially during the pandemic. Therefore, this nationwide study aimed to explore self-harm and suicide ideation and its predictive variables during the pandemic in Indonesia as a MIC with the highest COVID-19 fatality rate in Asia. Methods: Non-random sampling online survey was conducted nationwide between 25 May and 16 June</div></li>
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<ol start="2021" type="1">
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<li>The collected data were demographic variables (i.e. age group), loneliness from social isolation using The UCLA Loneliness Scale Six Items (ULS-6), and self-harm and suicide ideation using item 9 of The Patient Health Questionnaire-9 (PHQ-9). Predictive model was analyzed using hierarchical logistic regression. Results: A total of 5,211 participants from all 34 provinces in Indonesia completed the survey. Among 39.3% of them reported self-harm and suicide ideation during the pandemic, which significantly correlated with loneliness. The predictive variables associated with the likelihood of self-harm and suicide ideation were age, residence, job, religion, sex-gender, sexual orientation, HIV status, disability status, and loneliness. The predictive model showed a significant goodness-of-fit to the observed data (x2(15) = 1,803.46, p<.001), RN2 = .40. Conclusion: Four out of 10 Indonesians experienced self-harm and suicide ideation during the COVID-19 pandemic, particularly people within the age range of 18-24, living in the Java Island, unemployed/student/retired and freelancer, women, members of minority and marginalized communities, and experience of loneliness during the pandemic.
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🖺 Full Text HTML: <a href="https://psyarxiv.com/f3c8w/" target="_blank">Predicting self-harm and suicide ideation during the COVID-19 pandemic in Indonesia: A nationwide survey report</a>
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</div></li>
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</ol>
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<li><strong>Immediate myeloid depot for SARS-CoV-2 in the human lung</strong> -
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In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, considerable focus has been placed on a model of viral entry into host epithelial populations, with a separate focus upon the responding immune system dysfunction that exacerbates or causes disease. We developed a precision-cut lung slice model to investigate very early host-viral pathogenesis and found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations in the human lung. Infection of alveolar macrophages was partially dependent upon their expression of ACE2 and the infections were productive for amplifying virus, both findings which were in contrast with their neutralization of another pandemic virus, Influenza A virus (IAV). Compared to IAV, SARS-CoV-2 was extremely poor at inducing interferon-stimulated genes in infected myeloid cells, providing a window of opportunity for modest titers to amplify within these cells. Endotracheal aspirate samples from humans with COVID-19 confirmed the lung slice findings, revealing a persistent myeloid depot. In the early phase of SARS-CoV-2 infection, myeloid cells may provide a safe harbor for the virus with minimal immune stimulatory cues being generated, resulting in effective viral colonization and quenching of the immune system.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.28.489942v1" target="_blank">Immediate myeloid depot for SARS- CoV-2 in the human lung</a>
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</div></li>
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<li><strong>Occupational differences in SARS-CoV-2 infection: Analysis of the UK ONS Coronavirus (COVID-19) Infection Survey</strong> -
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Background Considerable concern remains about how occupational SARS-CoV-2 risk has evolved during the COVID-19 pandemic. We aimed to ascertain which occupations had the greatest risk of SARS-CoV-2 infection and explore how relative differences varied over the pandemic. Methods Analysis of cohort data from the UK Office of National Statistics Coronavirus (COVID-19) Infection Survey from April 2020 to November 2021. This survey is designed to be representative of the UK population and uses regular PCR testing. Cox and multilevel logistic regression to compare SARS-CoV-2 infection between occupational/sector groups, overall and by four time periods with interactions, adjusted for age, sex, ethnicity, deprivation, region, household size, urban/rural neighbourhood and current health conditions. Results Based on 3,910,311 observations from 312,304 working age adults, elevated risks of infection can be seen overall for social care (HR 1.14; 95% CI 1.04 to 1.24), education (HR 1.31; 95% CI 1.23 to 1.39), bus and coach drivers (1.43; 95% CI 1.03 to 1.97) and police and protective services (HR 1.45; 95% CI 1.29 to 1.62) when compared to non-essential workers. By time period, relative differences were more pronounced early in the pandemic. For healthcare elevated odds in the early waves switched to a reduction in the later stages. Education saw raises after the initial lockdown and this has persisted. Adjustment for covariates made very little difference to effect estimates. Conclusions Elevated risks among healthcare workers have diminished over time but education workers have had persistently higher risks. Long-term mitigation measures in certain workplaces may be warranted.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.28.22273177v1" target="_blank">Occupational differences in SARS-CoV-2 infection: Analysis of the UK ONS Coronavirus (COVID-19) Infection Survey</a>
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<li><strong>A bacteriophage-based, highly efficacious, needle and adjuvant-free, mucosal COVID-19 vaccine</strong> -
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The authorized mRNA- and adenovirus-based SARS-CoV-2 vaccines are intramuscularly injected and effective in preventing COVID-19, but do not induce efficient mucosal immunity, or prevent viral transmission. We developed a bacteriophage T4-based, multicomponent, needle and adjuvant-free, mucosal vaccine by engineering spike trimers on capsid exterior and nucleocapsid protein in the interior. Intranasal administration of T4-COVID vaccine induced higher virus neutralization antibody titers against multiple variants, balanced Th1/Th2 antibody and cytokine responses, stronger CD4+ and CD8+ T cell immunity, and higher secretory IgA titers in sera and bronchoalveolar lavage with no effect on the gut microbiota, compared to vaccination of mice intramuscularly. The vaccine is stable at ambient temperature, induces apparent sterilizing immunity, and provides complete protection against original SARS-CoV-2 strain and its Delta variant with minimal lung histopathology. This mucosal vaccine is an excellent candidate for boosting immunity of immunized and/or as a second-generation vaccine for the unimmunized population.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.28.489809v1" target="_blank">A bacteriophage-based, highly efficacious, needle and adjuvant-free, mucosal COVID-19 vaccine</a>
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</div></li>
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<li><strong>Systematic analysis of alternative splicing in time course data using Spycone</strong> -
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During disease progression or organism development, alternative splicing (AS) may lead to isoform switches (IS) that demonstrate similar temporal patterns and reflect the AS co-regulation of such genes. Tools for dynamic process analysis usually neglect AS. Here we propose Spycone (https://github.com/yollct/spycone), a splicing-aware framework for time course data analysis. Spycone exploits a novel IS detection algorithm and offers downstream analysis such as network and gene set enrichment. We demonstrate the performance of Spycone using simulated and real-world data of SARS- CoV-2 infection.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.28.489857v1" target="_blank">Systematic analysis of alternative splicing in time course data using Spycone</a>
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<li><strong>A Novel Y-Shaped, S-O-N-O-S-Bridged Crosslink between Three Residues C22, C44, and K61 Is a Redox Switch of the SARS-CoV-2 Main Protease</strong> -
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As the COVID-19 pathogen, SARS-CoV-2 relies on its main protease (MPro) for pathogenesis and replication. During the crystallographic analyses of MPro crystals that were exposed to the air, a uniquely Y-shaped, S-O-N-O-S-bridged posttranslational crosslink that connects three residues C22, C44, and K61 at their side chains was frequently observed. As a novel posttranslational modification, this crosslink serves as a redox switch to regulate the catalytic activity of MPro, a demonstrated drug target of COVID-19. The formation of this linkage leads to a much more opened active site that can be potentially targeted for the development of novel SARS-CoV-2 antivirals. The inactivation of MPro by this crosslink indicates that small molecules that lock MPro in the crosslinked form can be potentially used with other active site-targeting molecules such as paxlovid for synergistic effects in inhibiting the SARS-CoV-2 viral replication. Therefore, this new finding reveals a unique aspect of the SARS-CoV-2 pathogenesis and is potentially paradigm-shifting in our current understanding of the function of MPro and the development of its inhibitors as COVID-19 antivirals.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.04.29.490044v1" target="_blank">A Novel Y-Shaped, S-O-N-O-S-Bridged Crosslink between Three Residues C22, C44, and K61 Is a Redox Switch of the SARS-CoV-2 Main Protease</a>
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<li><strong>A Solution to the Kermack and McKendrick Integro-Differential Equations</strong> -
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In this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. The KMES can be cast in the form of a step function response to the input of new infections; and that response is the time series of the total infections. We demonstrate the veracity of the KMES using independent data from the Covid 19 pandemic and derive many previously unknown and useful analytical expressions for diagnosing and managing an epidemic. These include new expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections. Since the publication of the Kermack and McKendrick seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions which are putatively derived from the integro-differential equations, to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the more complex integro-differential equations, that the approximation adequately reproduces the dynamics of the integro-differential equations, and that herd immunity always exists. However, as we explicate in this manuscript, the KMES demonstrates that the SIR models are not adequate representations of the integro-differential equations, and herd immunity is not guaranteed. Our conclusion is that the KMES obsoletes the need for the SIR approximations; and provides a new level of understanding of epidemic dynamics.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.28.22274442v1" target="_blank">A Solution to the Kermack and McKendrick Integro-Differential Equations</a>
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<li><strong>Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination</strong> -
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Importance. Omicron is phylogenetically- and antigenically-distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron re-infection, and the added value of vaccination, require quantification. Objective. To estimate protection against Omicron re-infection and hospitalization conferred by prior heterologous SARS-CoV-2 (non-Omicron) infection and/or up to three doses of (ancestral, Wuhan-like) mRNA vaccine. Design. Test-negative study between December 26 (epi-week 52), 2021 and March 12 (epi-week 10), 2022. Setting. Population-based, province of Quebec, Canada Participants. Community-dwelling ≥12-year- olds tested for SARS-CoV-2. Exposures. Prior laboratory-confirmed infection with/without mRNA vaccination. Outcomes. Laboratory-confirmed SARS-CoV-2 re-infection and hospitalization, presumed Omicron by genomic surveillance. The odds of prior non-Omicron infection with/without vaccination were compared among Omicron cases/hospitalizations versus test- negative controls (single randomly-selected per individual). Adjusted odds ratios controlled for age, sex, testing- indication and epi-week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results. Without vaccination, prior non-Omicron infection reduced the Omicron re-infection risk by 44% (95%CI:38-48), decreasing from 66% (95%CI:57-73) at 3-5 months to 35% (95%CI:21-47) at 9-11 months post-infection and <30% thereafter. The more severe the prior infection, the greater the risk reduction: 8% (95%CI:17-28), 43% (95%CI:37-49) and 68% (95%CI:51-80) for prior asymptomatic, symptomatic ambulatory or hospitalized infections. mRNA vaccine effectiveness against Omicron infection was consistently significantly higher among previously-infected vs. non-infected individuals at 65% (95%CI:63-67) vs. 20% (95%CI:16-24) for one-dose; 68% (95%CI:67-70) vs. 42% (95%CI:41-44) for two doses; and 83% (95%CI:81-84) vs. 73% (95%CI:72-73) for three doses. Infection-induced protection against Omicron hospitalization was 81% (95%CI: 66-89) increasing to 86% (95%CI:77-99) with one, 94% (95%CI:91-96) with two and 97%(95%CI:94-99) with three mRNA vaccine doses. Two-dose effectiveness against hospitalization among previously-infected individuals did not wane across 11 months and did not significantly differ from three-dose effectiveness despite longer follow-up (median 158 and 27 days, respectively). Conclusions and relevance. Prior heterologous SARS-CoV-2 infection provided substantial and sustained protection against Omicron hospitalization, greatest among those also vaccinated. In the context of program goals to prevent severe outcomes and preserve healthcare system capacity, >2 doses of ancestral Wuhan-like vaccine may be of marginal incremental value to previously-infected individuals.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.29.22274455v1" target="_blank">Protection against Omicron re-infection conferred by prior heterologous SARS-CoV-2 infection, with and without mRNA vaccination</a>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PCR Testing in the UK During the SARS-CoV-2 Pandemic - Evidence from FOI Requests</strong> -
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Polymerase Chain Reaction (“PCR”) tests have been used to identify cases of COVID-19 during the course of the pandemic. Notably, PCR alone cannot differentiate between the presence of whole viruses (which can be transmitted and infect individuals) and small fragments of genetic material that are not infectious. A feature of PCR known as the cycle threshold (Ct) can be used to discriminate between these states, but the relationship between Ct and infectiousness is still poorly understood. This well-known limitation of the test compromises the identification of cases and their trends, and consequently those measures to interrupt transmission (such as isolation) that are undertaken on the basis of reliably identifying infectious individuals. Here, we interrogate the public authorities9 understanding of PCR testing for SARS-CoV-2 in the UK by accessing Freedom of Information requests submitted in 2020-21.We searched WhatDoTheyKnow and found 300 FOI requests, from over 150 individuals. We grouped their questions into four themes addressing the number of tests in use, the reporting of cycle thresholds (9Ct9), the Ct values themselves, and the accuracy of tests. The number of validated tests in use in the UK is currently not clear: In FOI responses, Public Health England (PHE) report it may be “80” or “85”. However, European regulations suggest there could be over 400 different CE marked tests available on the market and available for use. Laboratories have a statutory duty to report positive cases to PHE, but they do not have to advise which tests they are using nor submit Ct values. Only two FOI responses provided answers on Ct values, indicating that in a set time span, 24-38% of the Ct values were over 30. The most common FOI asked if there was a cycle threshold for positivity. In those that responded, the Ct for a positive result varied from 30 to 45. We found limited information on the technical accuracy of the tests. Several responses stated there is no 9static9, 9specific9 or 9standard9 cycle threshold. The current system requires significant changes to ensure it offers accurate diagnostic data to enable effective clinical management of SARS-CoV-2. PCR is an important and powerful tool, but its systematic misuse and misreporting risk undermining its usefulness and credibility.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.28.22274341v1" target="_blank">PCR Testing in the UK During the SARS-CoV-2 Pandemic - Evidence from FOI Requests</a>
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<li><strong>Understanding Definitions and Reporting of Deaths Attributed to COVID-19 in the UK - Evidence from FOI Requests</strong> -
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Death is a widely used outcome to assess the severity of pandemics. Accuracy in assigning the cause of death is of vital importance to define the impact of the agent, monitor its evolution, and compare its threat with those of other agents. Throughout the COVID-19 pandemic, there has been widespread reporting of aggregate death data with little attention paid to the accuracy of the assignment of causation. We aimed to analyse public authorities9 understanding of the assignment of cause of deaths during the SARS-CoV-2 pandemic in the UK by accessing Freedom of Information requests posed in three periods in 2020-21. By public authorities, we mean NHS Health Trusts, laboratories, and government agencies such as Public Health England and the Department of Health and Social Care. We searched WhatDoTheyKnow using the terms “covid and death”. We excluded those requests to bodies that cannot provide an answer (e.g. Councils) and those dealing with the effects of vaccines. We grouped questions into themes addressing the definitions and causes of death relevant to the pandemic. We looked at the responses to the questions of the definition of cause of death, the accuracy of the attribution, the role of other pre-existing pathologies and how these were reported and quantified. We found 800 requests from over 90 individuals. There was no consistency in the definition of cause of death or contributory cause of death across national bodies and in different bodies within the same nation. Nursing home providers, as well as medical practitioners, can assign a cause of death according to the Care Quality Commission. Post- mortem examinations were uncommon, the ONS did not incorporate their results in the summary of deaths by cause during the pandemic period. The meaning of the words “test” or “swab” was never clarified by any of the respondents. In care homes in England 1,304 out of 17,264 COVID-19 (7.6%, range 0% to 63%) mentioned COVID-19 in the absence of contributory or other factors in the death certificate, making it impossible to ascertain a chain of causality. The inconsistencies already noted hinder the ascertainment of the role of each factor leading to death and the quantification of the importance of infection. Some responses indicate that SARS-CoV-2 negative individuals or those whose death was not caused by COVID-19 were classified as “COVID-19 deaths”. We found 14 different ways of attributing the causes of death mentioned by respondents. The overall lack of consistency has confused the public and likely led to erroneous conclusions. We are unable to separate the effects on deaths of SARS-CoV-2 from those of human interventions. A coherent process based on consistent definitions across the devolved nations is required. Furthermore, to enhance the accuracy of causation in pandemics a subset of deaths should be verified using autopsies with full medical documentation.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.04.28.22274344v1" target="_blank">Understanding Definitions and Reporting of Deaths Attributed to COVID-19 in the UK - Evidence from FOI Requests</a>
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<li><strong>Intragenomic rearrangements of SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses</strong> -
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Variation of the betacoronavirus SARS-CoV-2 has been the bane of COVID-19 control. Documented variation includes point mutations, deletions, insertions, and recombination among closely or distantly related coronaviruses. Here, we describe yet another aspect of genome variation by beta- and alphacoronaviruses. Specifically, we report numerous genomic insertions of 5’-untranslated region sequences into coding regions of SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses. To our knowledge this is the first systematic description of such insertions. In many cases, these insertions change viral protein sequences and further foster genomic flexibility and viral adaptability through insertion of transcription regulatory sequences in novel positions within the genome. Among human Embecorivus betacoronaviruses, for instance, from 65% to all of the surveyed sequences in publicly available databases contain 5’-UTR-derived inserted sequences. In limited instances, there is mounting evidence that these insertions alter the fundamental biological properties of mutant viruses. Intragenomic rearrangements add to our appreciation of how variants of SARS-CoV-2 and other beta- and alphacoronaviruses may arise.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2022.03.07.483258v2" target="_blank">Intragenomic rearrangements of SARS-CoV-2, other betacoronaviruses, and alphacoronaviruses</a>
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<li><strong>Early Alveolar Epithelial Cell Necrosis is a Potential Driver of ARDS with COVID-19</strong> -
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Background Acute respiratory distress syndrome (ARDS) with COVID-19 is aggravated by hyperinflammatory responses even after the peak of viral load has passed; however, its underlying mechanisms remain unclear. Alveolar epithelial injury is reported to be a very early event in ARDS with COVID-19. Herein, we assessed whether necrosis of alveolar epithelial cells and subsequent releases of damage associated molecular patterns (DAMPs) at an early disease stage aggravates ARDS with COVID-19 Methods We analyzed the levels of cytokeratin18-M65, an epithelial total cell death marker; CK18-M30, an epithelial apoptosis-specific marker; and HMGB-1, one of the DAMPs released from necrotic cells, in patients with COVID-19 with and without ARDS and healthy adults, in addition to the circulating alveolar epithelial and endothelial injury markers, namely sRAGE, angiopoietin-2, and surfactant protein-D. Molecular mechanisms of alveolar epithelial cell death and effects of neutralization on alveolar tissue injury were assessed using a mouse model mimicking COVID-19-induced ARDS. Results COVID-19-induced ARDS was characterized by the elevation of sRAGE, an epithelial injury marker, at a very early disease stage. Although both serum levels of CK18-M65 and CK18-M30 were elevated in COVID-19-induced ARDS, the median CK18-M30/M65 ratio, an indicator of the fraction of apoptosis among total epithelial cell death, was 31.5% in serum from COVID-19 patients with ARDS, a value significantly lower than that of non-ARDS patients or healthy subjects. Moreover, the median M30/M65 ratio in bronchoalveolar lavage fluid (BALF) in COVID-19-induced ARDS was 27.8%, indicating that alveolar epithelial cell death is mainly caused by necrosis. Serum levels of HMGB-1 were also significantly elevated in ARDS versus non-ARDS patients. In a mouse model mimicking COVID-19-induced ARDS, the ratio of CK18-M30 to a total epithelial cell death marker in BALF was also lower than that in control subjects. Moreover, the alveolar epithelial cell necrosis involved two forms of programmed necrosis: necroptosis and pyroptosis. Finally, neutralization of HMGB-1 attenuated alveolar tissue injury in the mouse model. Conclusions Necrosis, including necroptosis and pyroptosis, seems to be the primary form of alveolar epithelial cell death and subsequent release of DAMPs is a potential driver of COVID-19-induced ARDS.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2022.01.23.22269723v2" target="_blank">Early Alveolar Epithelial Cell Necrosis is a Potential Driver of ARDS with COVID-19</a>
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<li><strong>Eradicate Coronavirus by blocking replication, counteracting its defense system</strong> -
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SIRT1 inhibitors can reduce replication of many viruses with certain similar characteristics to those of Coronaviruses, while p53 protein is another important factor in down-regulation of growth. There are some molecules that inhibit Sirtuin 1 and 2, in addition to activate p53 protein, by means of regulation of the interactions used by Coronaviruses as self-defense mechanism, degradating it. Even mTOR signal will be regulate, as well as autophagy will be inhibited, being this compound like a lysosomotropic agent. By blocking virus growth and continuous replication, associating the already tested Antiviral medicines, Covid-19 could be eradicated.
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🖺 Full Text HTML: <a href="https://thesiscommons.org/y4cbt/" target="_blank">Eradicate Coronavirus by blocking replication, counteracting its defense system</a>
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<li><strong>Eradicate Coronavirus by blocking replication, counteracting its defense system</strong> -
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SIRT1 inhibitors can reduce replication of many viruses with certain similar characteristics to those of Coronaviruses, while p53 protein is another important factor in down-regulation of growth. There are some molecules that inhibit Sirtuin 1 and 2, in addition to activate p53 protein, by means of regulation of the interactions used by Coronaviruses as self-defense mechanism, degradating it. Even mTOR signal will be regulate, as well as HIF-1α with the target genes and cytokines. Autophagy will be inhibited, being this compound like a lysosomotropic agent. By blocking virus growth and continuous replication, associating the already tested Antiviral medicines, Covid-19 could be eradicated.
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🖺 Full Text HTML: <a href="https://osf.io/psz35/" target="_blank">Eradicate Coronavirus by blocking replication, counteracting its defense system</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>Clinical Performance Evaluation of the Bio-Self™ COVID-19 Antigen Home Test</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Device: Bio-Self COVID-19 Antigen Home Test; Device: Standard of Care COVID-19 Test; Diagnostic Test: RT-PCR Test<br/><b>Sponsors</b>: BioTeke USA, LLC; CSSi Life Sciences<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>Immunogenicity and Safety of Fractional Booster Dose of COVID-19 Vaccines Available for Use in Pakistan/Brazil: A Phase 4 Dose-optimizing Trial</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: Sinovac; Biological: AZD1222; Biological: BNT162b2<br/><b>Sponsors</b>: Albert B. Sabin Vaccine Institute; Aga Khan University; Oswaldo Cruz Foundation; Stanford University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evaluate the Immunogenicity and Safety of a Recombinant Protein COVID-19 Vaccine as a Booster Dose in Population Aged 12-17 Years</strong> - <b>Conditions</b>: COVID-19; SARS-CoV-2 Infection<br/><b>Interventions</b>: Biological: SCTV01E; Biological: mRNA-1273<br/><b>Sponsor</b>: Sinocelltech Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A First-In-Human Phase 1b Study of AmnioPul-02 in COVID-19</strong> - <b>Condition</b>: COVID-19<br/><b>Intervention</b>: Drug: AmnioPul-02<br/><b>Sponsor</b>: Amniotics AB<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Older Adults.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety, Reactogenicity, and Immunogenicity Study of a Lyophilized COVID-19 mRNA Vaccine</strong> - <b>Condition</b>: Covid19<br/><b>Interventions</b>: Biological: A Lyophilized COVID-19 mRNA Vaccine; Biological: Placebo<br/><b>Sponsor</b>: Jiangsu Rec-Biotechnology Co., Ltd.<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of COVID-19 mRNA Vaccine (SYS6006) in Chinese Healthy Adults Aged 18 -59 Years.</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Biological: 20 μg dose of SYS6006; Biological: 30 μg dose of SYS6006; Biological: 50 μg dose of SYS6006; Drug: Placebo<br/><b>Sponsor</b>: <br/>
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CSPC ZhongQi Pharmaceutical Technology Co., Ltd.<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients</strong> - <b>Condition</b>: COVID-19 Pneumonia<br/><b>Interventions</b>: Drug: NuSepin® 0.2 mg/kg; Drug: NuSepin® 0.4 mg/kg; Drug: Placebo<br/><b>Sponsor</b>: Shaperon<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>Aerobic Exercise and Covid-19 Survivors With Post-Intensive Care Syndrome (Pics)</strong> - <b>Conditions</b>: COVID-19; Post Intensive Care Syndrome<br/><b>Interventions</b>: <br/>
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Other: Aerobic Exercise Training; Other: Home Plan<br/><b>Sponsor</b>: Riphah International University<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Efficacy and Safety of JT001 (VV116) Compared With Paxlovid</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Drug: JT001; Drug: Paxlovid<br/><b>Sponsor</b>: <br/>
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Vigonvita Life Sciences<br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles as Early Goal Directed Therapy for COVID-19 Moderate-to-Severe Acute Respiratory Distress Syndrome (ARDS): A Phase III Clinical Trial</strong> - <b>Condition</b>: COVID-19 Acute Respiratory Distress Syndrome<br/><b>Intervention</b>: Drug: EXOFLO<br/><b>Sponsor</b>: Direct Biologics, LLC<br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Use of Continuous Glucose Monitors in Coronavirus Disease 2019 ICU and Potential Inpatient Settings</strong> - <b>Conditions</b>: Covid19; Diabetes Mellitus<br/><b>Intervention</b>: Device: continuous glucose monitoring<br/><b>Sponsor</b>: Tanureet K Arora<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>Phase Ⅱ Clinical Trial of SARS-CoV-2 mRNA Vaccine</strong> - <b>Condition</b>: SARS-CoV-2<br/><b>Interventions</b>: Biological: SARS-CoV-2 (LVRNA009) 50μg group; Biological: SARS-CoV-2 (LVRNA009) 100μg group; Other: Placebo<br/><b>Sponsors</b>: AIM Vaccine Co., Ltd.; Hunan Provincial Center for Disease Control and Prevention<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>Sample Collection for Evaluation of the Panbio™ COVID-19/ Flu A&B Rapid Panel.</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B<br/><b>Intervention</b>: Diagnostic Test: Nasal and Nasopharyngeal Sampling of the Panbio™ COVID-19/ Flu A&B Rapid Panel<br/><b>Sponsor</b>: Abbott Rapid Dx<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>Pilot Trial on Immunosuppression Modulation to Increase SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients</strong> - <b>Condition</b>: COVID-19<br/><b>Interventions</b>: Other: Immunosuppression reduction; Other: No immunosuppression reduction<br/><b>Sponsor</b>: Medical University of Vienna<br/><b>Active, not 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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A raising dawn of pentoxifylline in management of inflammatory disorders in Covid-19</strong> - The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up- regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The determination of haemagglutinin influenza antibodies in the Polish population in the epidemic season 2020/2021 during the SARS-CoV-2 pandemic</strong> - The aim of the study was to prove the level of antibodies against haemagglutinin in the sera of people from seven age groups in the epidemic season 2020/2021 in Poland to determine the differentiation of the antibody level and the protection rate depending on age. The level of anti-haemagglutinin antibodies was established by haemagglutinin inhibition test (HAI). A total of 700 randomly selected sera from people belonging to 7 different age groups were tested. The results confirmed the presence…</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>Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti- SARS-CoV-2 Agents</strong> - Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A ( 1 ) and oridonin ( 2 ) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1 . Further mechanistic study suggested a concerted mechanism for…</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>Inflammasome activation in infected macrophages drives COVID-19 pathology</strong> - Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response all of which are recapitulated and required for pathology in the SARS-CoV-2 infected MISTRG6-hACE2 humanized mouse model of COVID-19 with a human immune system^(1-20). Blocking either viral replication with Remdesivir^(21-23) or the downstream IFN stimulated cascade with anti-IFNAR2 in vivo in the chronic stages of disease attenuated 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>Recent advances in passive immunotherapies for COVID-19: The Evidence-Based approaches and clinical trials</strong> - In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing a global pandemic called COVID-19. Currently, there is no definitive treatment for this emerging disease. Global efforts resulted in developing multiple platforms of COVID-19 vaccines, but their efficacy in humans should be wholly investigated in the long-term clinical and epidemiological follow-ups. Despite the international efforts, COVID-19 vaccination accompanies challenges, including financial 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>Mutations in the SARS-CoV-2 RNA dependent RNA polymerase confer resistance to remdesivir by distinct mechanisms</strong> - The nucleoside analog remdesivir (RDV) is a Food and Drug Administration (FDA)-approved antiviral for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Thus, it is critical to understand factors that promote or prevent RDV resistance. We passaged SARS-CoV-2 in the presence of increasing concentrations of GS-441524, the parent nucleoside of RDV. After 13 passages, we isolated three viral lineages with phenotypic resistance as defined by increases in…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A multifunctional colorimetric sensor array for bacterial identification and real-time bacterial elimination to prevent bacterial contamination</strong> - Effective identification and real-time inactivation of pathogenic microorganisms is of great importance for preventing their infection and spread in public health, especially considering the huge threat of coronavirus disease 2019 (COVID-19). Herein, a novel multifunctional colorimetric sensor array with 3,3’,5,5’-tetramethylbenzidine (TMB) as a single probe has been constructed. TMB can be efficiently oxidized to generate oxidized TMB (oxTMB) by HAuCl(4), which displays four characteristic…</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>Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease</strong> - The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites 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>Versisterol, a new endophytic steroid with 3CL protease inhibitory activity from <em>Avicennia marina</em> (Forssk.) Vierh</strong> - A new epoxy ergostane sterol, named versisterol, was isolated from Aspergillus versicolor, an endophytic fungus from Avicennia marina. The structure of the isolated compound was deduced by means of one- and two-dimensional NMR and high- resolution mass spectrometry. The absolute stereochemistry was elucidated by NOESY analysis, and experimental and calculated time-dependent density functional theory (TD-DFT) circular dichroism spectroscopy. Versisterol inhibited 3CL protease (3CL^(pro)) with an…</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><em>In silico</em> study of the inhibition of SARS-COV-2 viral cell entry by neem tree extracts</strong> - The outbreak of COVID-19, caused by SARS-COV-2, is responsible for higher mortality and morbidity rates across the globe. Until now, there is no specific treatment of the disease and hospitalized patients are treated according to the symptoms they develop. Efforts to identify drugs and/or vaccines are ongoing processes. Natural products have shown great promise in the treatment of many viral related diseases. In this work, using in silico methods, bioactive compounds from the neem tree were…</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>Two novel oxetane containing lignans and a new megastigmane from <em>Paronychia arabica</em> and <em>in silico</em> analysis of them as prospective SARS-CoV-2 inhibitors</strong> - The chemical characterization of the extract of the aerial parts of Paronychia arabica afforded two oxetane containing lignans, paronychiarabicine A (1) and B (2), and one new megastigmane, paronychiarabicastigmane A (3), alongside a known lignan (4), eight known phenolic compounds (5-12), one known elemene sesquiterpene (13) and one steroid glycoside (14). The chemical structures of the isolated compounds were constructed based upon the HRMS, 1D, and 2D-NMR results. The absolute configurations…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The interactions of folate with the enzyme furin: a computational study</strong> - Entrance of coronavirus into cells happens through the spike proteins on the virus surface, for which the spike protein should be cleaved into S1 and S2 domains. This cleavage is mediated by furin, a member of the proprotein convertases family, which can specifically cleave Arg-X-X-Arg↓ sites of the substrates. Here, folate (folic acid), a water-soluble B vitamin, is introduced for the inhibition of furin activity. Therefore, molecular insight into the prevention of furin activity in 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>Drug repurposing and computational modeling for discovery of inhibitors of the main protease (M<sup>pro</sup>) of SARS-CoV-2</strong> - The main protease (M^(pro) or 3CL^(pro)) is a conserved cysteine protease from the coronaviruses and started to be considered an important drug target for developing antivirals, as it produced a deadly outbreak of COVID-19. Herein, we used a combination of drug reposition and computational modeling approaches including molecular docking, molecular dynamics (MD) simulations, and the calculated binding free energy to evaluate a set of drugs in complex with the M^(pro) enzyme. Particularly, our…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural coumarins as potential anti-SARS-CoV-2 agents supported by docking analysis</strong> - COVID-19 is a global pandemic first identified in China, causing severe acute respiratory syndrome. One of the therapeutic strategies for combating viral infections is the search for viral spike proteins as attachment inhibitors among natural compounds using molecular docking. This review aims at shedding light on the antiviral potential of natural products belonging to the natural-products class of coumarins up to 2020. Moreover, all these compounds were filtered based on ADME analysis to…</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>Long-term immunological consequences of anti-CD20 therapies on humoral responses to COVID-19 vaccines in multiple sclerosis: an observational study</strong> - CONCLUSION: Anti-CD20-induced inhibition of humoral responses to COVID-19 vaccines is transient and antibody production was more pronounced >18 months after anti-CD20 treatment discontinuation. The immunological effect on B-cell counts appears to wane by the same time.</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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