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167 lines
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<title>20 January, 2024</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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<ul>
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<li><strong>Mis- and Disinformation during the 2021 Canadian Federal Election</strong> -
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<div>
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The Canadian Election Misinformation Project was a civil society and academic partnership that aimed to rapidly identify and respond to mis- and disinformation incidents during the 44th Canadian Federal Election while evaluating the extent to which these incidents impact the attitudes and behaviours of Canadians. It also sought to develop understanding of the types and consequences of misleading and false information circulating in the public sphere in addition to supporting world-class research into the dynamics of the information ecosystem and the broad impacts of misinformation on Canadian democracy. The data shows that: 1) Although there was widespread misinformation during the 2021 Canadian federal election, the overall election was minimally impacted by mis- and disinformation; 2) Most Canadians believe the election was safe from foreign interference and that misinformation played a minimal role in the election; 3) Communities that previously focused on sharing COVID-19 misinformation adopted conspiracy theories about a broader set of topics during the election, including vaccines, climate change, and the integrity of the election; and 4) Nevertheless, a strong majority of Canadians believe that misinformation is a threat to Canadian democracy, polarizes Canadians, and threatens social cohesion.
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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://osf.io/ubfmx/" target="_blank">Mis- and Disinformation during the 2021 Canadian Federal Election</a>
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</div></li>
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<li><strong>Public Health Communication and Engagement on Social Media during the COVID-19 Pandemic</strong> -
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<div>
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Social media provides governments the opportunity to directly communicate with their constituents. During a pandemic, reaching as many citizens as possible with health messaging is critical to reducing the spread of the disease. This study evaluates efforts to spread healthcare information by Canadian local, provincial, and federal governments during the first five months of the COVID-19 pandemic. We collect all health-related communications coming from government accounts on Facebook and Twitter and analyze the data using a nested mixed method approach. We first identify quantifiable features linked with citizen engagement, before subsequently performing content analysis on outlier posts. We make two critical contributions to existing knowledge about government communication, particularly during public health crises. We identify cross-platform variations in strategy effectiveness and draw attention to specific, evidence-based practices that can increase engagement with government health information.
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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://osf.io/7hypj/" target="_blank">Public Health Communication and Engagement on Social Media during the COVID-19 Pandemic</a>
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</div></li>
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<li><strong>All in this together: deservingness of government aid during the COVID-19 pandemic</strong> -
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<div>
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The COVID-19 pandemic has placed unprecedented pressure on governments to engage in widespread cash transfers directly to citizens to help mitigate economic losses. These programs are major redistribution efforts aimed at a variety of sub-groups within society (the unemployed, those with children, those with pre-existing health conditions, etc.) and there has been remarkably little resistance to these government outlays. We employ a novel and pre-registered paired vignette experiment to assess support for government aid during the pandemic in a large, nationally representative sample. We evaluate whether the “normal” deservingness hierarchy and considerations of social affinity or material self-interest continue to drive preferences of Canadians regarding redistribution. We find only small deservingness considerations and little evidence that redistribution preferences are informed by similarity considerations. Instead, we find broad, generous, and non-discriminatory support for direct cash transfers during this period of crisis.
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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://osf.io/eyvhj/" target="_blank">All in this together: deservingness of government aid during the COVID-19 pandemic</a>
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</div></li>
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<li><strong>The Causes and Consequences of COVID-19 Misperceptions: Understanding the Role of News and Social Media</strong> -
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<div>
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We investigate the relationship between media consumption, misinformation, and important attitudes and behaviours during the COVID-19 pandemic in Canada. We find that comparatively more misinformation circulates on social media platforms, while traditional news media tend to reinforce public health recommendations like social distancing. We find that exposure to social media is associated with misperceptions about COVID-19 while the inverse is true for news media. These misperceptions are in turn associated with lower compliance with social distancing measures. We thus draw a link from misinformation on social media to behaviours and attitudes that potentially magnify the scale and lethality of COVID-19.
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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://osf.io/6tcdn/" target="_blank">The Causes and Consequences of COVID-19 Misperceptions: Understanding the Role of News and Social Media</a>
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</div></li>
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<li><strong>The lasting earnings losses of COVID-19 short-time work</strong> -
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<div>
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This study is the first to investigate the impact of short-time work (STW) schemes during the COVID-19 pandemic on earnings after STW. STW schemes were implemented to preserve employee–employer matches, support workers’ incomes, and uphold consumption. Although workers faced temporary earnings losses under STW, it is unclear if the negative earnings effects of STW persisted or were limited to the STW spell. Therefore, this study uses a dynamic difference-in-difference (DiD) identification strategy with administrative data to identify any lasting STW effects on earnings. This approach accounts for factors that influenced worker selection into STW and tests for heterogeneous effects across subgroups of workers. We find lasting earnings losses that persisted beyond the STW participation itself. Most importantly, these earnings losses depended on the duration of STW exposure, with greater negative effects being more prominent in cases of long-term or recurring STW spells. Lasting, post-STW earnings losses tended to be more pronounced for white-collar jobs, while the largest losses were observed among men with blue-collar jobs whose STW spells exceeded one year.
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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://osf.io/preprints/socarxiv/p2qvh/" target="_blank">The lasting earnings losses of COVID-19 short-time work</a>
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</div></li>
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<li><strong>Revealing the drivers of antibiotic resistance trends in Streptococcus pneumoniae amidst the 2020 COVID-19 pandemic: Insights from mathematical modeling</strong> -
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<div>
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Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built in into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.
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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/10.1101/2022.08.08.503267v4" target="_blank">Revealing the drivers of antibiotic resistance trends in Streptococcus pneumoniae amidst the 2020 COVID-19 pandemic: Insights from mathematical modeling</a>
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</div></li>
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<li><strong>Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water</strong> -
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<div>
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The COVID-19 pandemic illustrates the importance of understanding the behavior and control of human pathogenic viruses in the environment. Exposure via water (drinking, bathing, and recreation) is a known route of transmission of viruses to humans, but the literature is relatively void of studies on the persistence of many viruses, especially coronaviruses, in water and their susceptibility to chlorine disinfection. To fill that knowledge gap, we evaluated the persistence and free chlorine disinfection of human coronavirus OC43 (HCoV-OC43) and its surrogates, murine hepatitis virus (MHV) and porcine transmissible gastroenteritis virus (TGEV), in drinking water and laboratory buffer using cell culture methods. The decay rate constants of human coronavirus and its surrogates in water varied depending on virus and water matrix. In drinking water prior to disinfectant addition, MHV showed the largest decay rate constant (2.25 day-1) followed by HCoV-OC43 (0.99 day-1) and TGEV (0.65 day-1); while in phosphate buffer, HCoV-OC43 (0.51 day-1) had a larger decay rate constant than MHV (0.28 day-1) and TGEV (0.24 day-1). Upon free chlorine disinfection, the inactivation rates of coronaviruses were independent of free chlorine concentration and not affected by water matrix, though they still varied between viruses. TGEV showed the highest susceptibility to free chlorine disinfection with the inactivation rate constant of 113.50 mg-1 min-1 L, followed by MHV (81.33 mg-1 min-1 L) and HCoV-OC43 (59.42 mg-1 min-1 L).
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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/10.1101/2024.01.16.575911v1" target="_blank">Persistence and Free Chlorine Disinfection of Human Coronaviruses and Their Surrogates in Water</a>
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</div></li>
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<li><strong>A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model</strong> -
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<div>
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Yersinia pestis, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, Y. pestis is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug resistant strains. The dissemination of such Y. pestis strains could be catastrophic, with public health consequences far more daunting than those caused by the recent COVID-19 pandemic. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing Y. pestis infections. This includes infections by antigenically distinct strains for which vaccines, none FDA approved yet, may not be effective, and those that cannot be controlled by approved antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation with a 100% lytic activity against a panel of 68 genetically diverse Y. pestis strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 hours post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies suggest that YPP-401 could provide an innovative, safe, and effective approach for managing Y. pestis infections, including those caused by naturally occurring or intentionally developed strains that cannot be managed by vaccines in development and antibiotics.
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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/10.1101/2024.01.17.576055v1" target="_blank">A Bacteriophage Cocktail Targeting Yersinia pestis Provides Strong Post-Exposure Protection in a Rat Pneumonic Plague Model</a>
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</div></li>
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<li><strong>GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</strong> -
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<div>
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Glycosylation of the SARS-CoV-2 spike (S) protein represents a key target for viral evolution because it affects both viral evasion and fitness. Successful variations in the glycan shield are difficult to achieve though, as protein glycosylation is also critical to folding and to structural stability. Within this framework, the identification of glycosylation sites that are structurally dispensable can provide insight into the evolutionary mechanisms of the shield and inform immune surveillance. In this work we show through over 45 s of cumulative sampling from conventional and enhanced molecular dynamics (MD) simulations, how the structure of the immunodominant S receptor binding domain (RBD) is regulated by N-glycosylation at N343 and how the structural role of this glycan changes from WHu-1, alpha (B.1.1.7), and beta (B.1.351), to the delta (B.1.617.2) and omicron (BA.1 and BA.2.86) variants. More specifically, we find that the amphipathic nature of the N-glycan is instrumental to preserve the structural integrity of the RBD hydrophobic core and that loss of glycosylation at N343 triggers a specific and consistent conformational change. We show how this change allosterically regulates the conformation of the receptor binding motif (RBM) in the WHu-1, alpha and beta RBDs, but not in the delta and omicron variants, due to mutations that reinforce the RBD architecture. In support of these findings, we show that the binding of the RBD to monosialylated ganglioside co-receptors is highly dependent on N343 glycosylation in the WHu-1, but not in the delta RBD, and that affinity changes significantly across VoCs. Ultimately, the molecular and functional insight we provide in this work reinforces our understanding of the role of glycosylation in protein structure and function and it also allows us to identify the structural constraints within which the glycosylation site at N343 can become a hotspot for mutations in the SARS-CoV-2 S glycan shield.
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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/10.1101/2023.12.05.570076v2" target="_blank">GotGlycans: Role of N343 Glycosylation on the SARS-CoV-2 S RBD Structure and Co-Receptor Binding Across Variants of Concern</a>
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</div></li>
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<li><strong>Phase 1 of the NIH Preprint Pilot: Testing the viability of making preprints discoverable in PubMed Central and PubMed</strong> -
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<div>
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Introduction: The National Library of Medicine (NLM) launched a pilot in June 2020 to 1) explore the feasibility and utility of adding preprints to PubMed Central (PMC) and making them discoverable in PubMed and 2) to support accelerated discoverability of NIH-supported research without compromising user trust in NLM’s widely used literature services. Methods: The first phase of the Pilot focused on archiving preprints reporting NIH-supported SARS-CoV-2 virus and COVID-19 research. To launch Phase 1, NLM identified eligible preprint servers and developed processes for identifying NIH-supported preprints within scope in these servers. Processes were also developed for the ingest and conversion of preprints in PMC and to send corresponding records to PubMed. User interfaces were modified for display of preprint records. NLM collected data on the preprints ingested and discovery of preprint records in PMC and PubMed and engaged users through focus groups and a survey to obtain direct feedback on the Pilot and perceptions of preprints. Results: Between June 2020 and June 2022, NLM added more than 3,300 preprint records to PMC and PubMed, which were viewed 4 million times and 3 million times, respectively. Nearly a quarter of preprints in the Pilot were not associated with a peer-reviewed published journal article. User feedback revealed that the inclusion of preprints did not have a notable impact on trust in PMC or PubMed. Discussion: NIH-supported preprints can be identified and added to PMC and PubMed without disrupting existing operations processes. Additionally, inclusion of preprints in PMC and PubMed accelerates discovery of NIH research without reducing trust in NLM literature services. Phase 1 of the Pilot provided a useful testbed for studying NIH investigator preprint posting practices, as well as knowledge gaps among user groups, during the COVID-19 public health emergency, an unusual time with heightened interest in immediate access to research results.
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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/10.1101/2022.12.12.520156v2" target="_blank">Phase 1 of the NIH Preprint Pilot: Testing the viability of making preprints discoverable in PubMed Central and PubMed</a>
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</div></li>
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<li><strong>Deciphering the Molecular Mechanism of Post-Acute Sequelae of COVID-19 through Comorbidity Network Analysis</strong> -
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<div>
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Introduction: The post-acute sequelae of COVID-19 presents a significant health challenge in the post-pandemic world. Our study aims to analyze longitudinal electronic health records to determine the impact of COVID-19 on disease progression, provide molecular insights into these mechanisms, and identify associated biomarkers. Method: We included 58,710 patients with COVID-19 records from 01/01/2020 to 31/08/2022 and at least one hospital admission before and after the acute phase of COVID-19 (28 days) as the treatment group. A healthy control group of 174,071 individuals was established for comparison using propensity score matching based on pre-existing diseases (before COVID-19). We built a comorbidity network using Pearson correlation coefficient differences between pairs of pre-existing disease and post-infection disease in both groups. Disease-protein mapping and protein-protein interaction network analysis revealed the impact of COVID-19 on disease trajectories through protein interactions in the human body. Results: The disparity in the weight of prevalent disease comorbidity patterns between the treatment and control groups highlights the impact of COVID-19. Certain specific comorbidity patterns show a more pronounced influence by COVID-19. For each comorbidity pattern, overlapping proteins directly associated with pre-existing diseases, post-infection diseases, and COVID-19 help to elucidate the biological mechanism of COVID-19's impact on each comorbidity pattern. Proteins essential for explaining the biological mechanism can be identified based on their weights. Conclusion: Disease comorbidity associations influenced by COVID-19, as identified through longitudinal electronic health records and disease-protein mapping, can help elucidate the biological mechanisms of COVID-19, discover intervention methods, and decode the molecular basis of comorbidity associations. This analysis can also yield potential biomarkers and corresponding treatments for specific disease patterns.
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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/10.1101/2024.01.17.575851v1" target="_blank">Deciphering the Molecular Mechanism of Post-Acute Sequelae of COVID-19 through Comorbidity Network Analysis</a>
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</div></li>
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<li><strong>Changes in wild meat hunting and use by rural communities during the COVID-19 socio-economic shock</strong> -
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<div>
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There has been limited quantitative research into the effects of socio-economic shocks on biological resource use. Focusing on wild meat hunting, a substantial livelihood and food source in tropical regions, we evaluated the impacts of the shock from Nigeria’s COVID-19 lockdown on species exploitation around a global biodiversity hotspot. Using a three-year quantitative dataset collected during and after the lockdown (covering 1,008 hunter-months) and matching by time of year, we found that successful hunting trip rates were more frequent during lockdown, with a corresponding increase in the monthly number, mass, and value of animals caught. Moreover, hunters consumed a larger proportion of wild meat and sold less during lockdown compared to non-lockdown periods. These results suggest that local communities relied on wild meat to supplement reduced food and income during lockdown, buffering COVID-19’s socio-economic shock. Our findings also indicate that wild species may be especially vulnerable to increased hunting pressure during such shocks.
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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://osf.io/ezyr7/" target="_blank">Changes in wild meat hunting and use by rural communities during the COVID-19 socio-economic shock</a>
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</div></li>
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<li><strong>Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection</strong> -
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<div>
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Inflammation-induced thrombosis is a common consequence of bacterial and viral infections, such as those caused by Salmonella Typhimurium (STm) and SARS-CoV-2. The identification of multi-organ thrombosis and the chronological differences in its induction and resolution raise significant challenges for successfully targeting multi-organ infection-associated thrombosis. Here, we identified specific pathways and effector cells driving thrombosis in the spleen and liver following STm infection. Thrombosis in the spleen is independent of IFN-{gamma} or the platelet C-type lectin-like receptor CLEC-2, while both molecules were previously identified as key drivers of thrombosis in the liver. Furthermore, we identified platelets, monocytes, and neutrophils as core constituents of thrombi in both organs. Depleting neutrophils or monocytic cells independently abrogated thrombus formation. Nevertheless, blocking TNF, which is expressed by both myeloid cell types, diminished both thrombosis and inflammation which correlates with reduced endothelial expression of E-selectin and leukocyte infiltration. Moreover, tissue factor and P-selectin glycoprotein ligand 1 inhibition impairs thrombosis in both spleen and liver, identifying multiple common checkpoints to target multi-organ thrombosis. Therefore, organ-specific, and broad mechanisms driving thrombosis potentially allow tailored treatments based on the clinical need and to define the most adequate strategy to target both thrombosis and inflammation associated with systemic infections.
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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/10.1101/2024.01.16.575813v1" target="_blank">Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection</a>
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</div></li>
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<li><strong>Impact of SARS-CoV-2 spike efficacy on tolerability of spike-based Covid-19 Vaccinations</strong> -
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<div>
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Abstract: Knowledge about the efficacy of vaccine spikes has multiplied in recent years. The purpose of this review is to update the key findings from the scientific literature that provide explanations for many of the reported and analysed adverse effects associated with the spike-based Covid-19 vaccination. Principle results: An overwhelming body of evidence supports the main mode of action of spike-based Covid-19 vaccines, namely the downregulation of ACE2 by spikes. Direct spike effects, synergisms and RAAS-independent responses complement and multiply the already deleterious effects on tolerability. It has been repeatedly confirmed that the SARS-CoV spike protein alone is not only able to downregulate ACE2, but also to induce cell fusion, activation of TLR4, of co-receptors and gastrointestinal responses. The systemic and long-lasting detection of spikes after vaccination disproves the claimed regionally limited and short-lasting spike production and efficacy. The production volume of spikes, their dependencies and the non-neutralised spike proportion have so far remained unknown for unknown reasons. Conclusions: The exceptionally broad spectrum, frequency and severity of the reported side effects associated with spike-based Covid-19 vaccination exceed the known level of conventional vaccinations. According to my side effect analyses, the spike-based vaccines possess an unacceptable class-specific, unique side effect profile. From a pharmacological point of view, spikes are highly active substances, but not tolerable simple antigens. For this reason, they are not suitable for preventive immunisation to avoid comparatively harmless infections.
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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://osf.io/pw8zr/" target="_blank">Impact of SARS-CoV-2 spike efficacy on tolerability of spike-based Covid-19 Vaccinations</a>
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</div></li>
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<li><strong>Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody</strong> -
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<div>
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Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus interventions for effective pandemic preparedness. Here, using LIBRA-seq, we report a panel of 50 coronavirus antibodies isolated from human B cells. Of these antibodies, 54043-5 was shown to bind the S2 subunit of spike proteins from alpha-, beta-, and deltacoronaviruses. A cryo-EM structure of 54043-5 bound to the pre-fusion S2 subunit of the SARS-CoV-2 spike defined an epitope at the apex of S2 that is highly conserved among betacoronaviruses. Although non-neutralizing, 54043-5 induced Fc-dependent antiviral responses, including ADCC and ADCP. In murine SARS-CoV-2 challenge studies, protection against disease was observed after introduction of Leu234Ala, Leu235Ala, and Pro329Gly (LALA-PG) substitutions in the Fc region of 54043-5. Together, these data provide new insights into the protective mechanisms of non-neutralizing antibodies and define a broadly conserved epitope within the S2 subunit.
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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/10.1101/2024.01.15.575741v1" target="_blank">Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody</a>
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</div></li>
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</ul>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</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>Diet and Fasting for Long COVID</strong> - <b>Conditions</b>: Long Covid19; Long COVID <br/><b>Interventions</b>: Other: Low sugar diet and 10-12 hour eating window; Other: Low sugar diet, 8 hour eating window and fasting <br/><b>Sponsors</b>: Pacific Northwest University of Health 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>The Effectiveness of a Health Promotion Program for Older People With Post-Covid-19 Sarcopenia</strong> - <b>Conditions</b>: Post COVID-19 Condition <br/><b>Interventions</b>: Other: Protein powder and Resistance exercise <br/><b>Sponsors</b>: Mahidol University; National Health Security Office, Thailand <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>Chronic-disease Self-management Program in Patients Living With Long-COVID in Puerto Rico</strong> - <b>Conditions</b>: Long Covid19 <br/><b>Interventions</b>: Other: “Tomando control de su salud” (Spanish Chronic Disease Self-Management) <br/><b>Sponsors</b>: University of Puerto Rico; National Institutes of Health (NIH) <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>Treatment of Persistent Post-Covid-19 Smell and Taste Disorders</strong> - <b>Conditions</b>: Post-covid-19 Persistent Smell and Taste Disorders <br/><b>Interventions</b>: Drug: Cerebrolysin; Other: olfactory and gustatory trainings <br/><b>Sponsors</b>: Sherifa Ahmed Hamed <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Evealuate Safety and Immunogenicity of TI-0010 SARS-CoV-2 Vaccine in Healthy Adults</strong> - <b>Conditions</b>: COVID-19; COVID-19 Immunisation <br/><b>Interventions</b>: Biological: TI-0010; Biological: Placebo <br/><b>Sponsors</b>: National Drug Clinical Trial Institute of the Second Affiliated Hospital of Bengbu Medical College; Therorna <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>Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction</strong> - <b>Conditions</b>: Long Haul COVID-19; Post-Acute COVID-19 Syndrome; Anosmia; Olfaction Disorders <br/><b>Interventions</b>: Drug: Sodium Citrate; Drug: Normal Saline; Other: Olfactory Training Kit - “The Olfactory Kit, by AdvancedRx” <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill <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 II, Double Blind, Randomized Trial of CX-4945 in Viral Community Acquired Pneumonia</strong> - <b>Conditions</b>: Community-acquired Pneumonia; SARS-CoV-2 -Associated Pneumonia; Influenza With Pneumonia <br/><b>Interventions</b>: Drug: CX-4945 (SARS-CoV-2 domain); Drug: Placebo (SARS-CoV-2 domain); Drug: CX-4945 (Influenza virus domain); Drug: Placebo (Influenza virus domain) <br/><b>Sponsors</b>: Senhwa Biosciences, Inc. <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>Edge AI-deployed DIGItal Twins for PREDICTing Disease Progression and Need for Early Intervention in Infectious and Cardiovascular Diseases Beyond COVID-19 - Investigation of Biomarkers in Dermal Interstitial Fluid</strong> - <b>Conditions</b>: Heart Failure <br/><b>Interventions</b>: Device: Use of the PELSA System for dISF extraction <br/><b>Sponsors</b>: Charite University, Berlin, Germany <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>Phase III Clinical Study Evaluating the Efficacy and Safety of WPV01 in Patients With Mild/Moderate COVID-19</strong> - <b>Conditions</b>: Mild to Moderate COVID-19 <br/><b>Interventions</b>: Drug: WPV01; Drug: Placebo <br/><b>Sponsors</b>: Westlake Pharmaceuticals (Hangzhou) 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>Integrated Mindfulness-based Health Qigong Intervention for COVID-19 Survivors and Caregivers</strong> - <b>Conditions</b>: COVID-19 Infection <br/><b>Interventions</b>: Other: Mindfulness-based Health Qigong Intervention <br/><b>Sponsors</b>: The Hong Kong Polytechnic University <br/><b>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>Analyzing the impact of COVID-19 on consumption behaviors through recession and recovery patterns</strong> - The COVID-19 outbreak has dramatically impacted the economy, particularly consumption behaviors. Studies on how consumption responses to COVID-19 can be a powerful aid for urban consumption recovery. In this paper, based on a high-frequency consumption dataset from January 6, 2020, to April 28, 2020 covering 18 sectors and dataset from the corresponding lunar period in 2021, we look at how COVID-19 changed how people spent their money by looking at patterns of recession and recovery during 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>Informatics and Computational Approaches for the Discovery and Optimization of Natural Product-Inspired Inhibitors of the SARS-CoV-2 2’-<em>O</em>-Methyltransferase</strong> - The urgent need for new classes of orally available, safe, and effective antivirals─covering a breadth of emerging viruses─is evidenced by the loss of life and economic challenges created by the HIV-1 and SARS-CoV-2 pandemics. As frontline interventions, small-molecule antivirals can be deployed prophylactically or postinfection to control the initial spread of outbreaks by reducing transmissibility and symptom severity. Natural products have an impressive track record of success as prototypic…</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>Identifying novel inhibitors targeting Exportin-1 for the potential treatment of COVID-19</strong> - The nuclear export protein 1 (XPO1) mediates the nucleocytoplasmic transport of proteins and ribonucleic acids (RNAs) and plays a prominent role in maintaining cellular homeostasis. XPO1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses. In our earlier study, we proved the inhibition of XPO1 as a therapeutic strategy for managing SARS-COV-2 and its variants. In this study, we have utilized pharmacophore-assisted computational methods to identify…</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>Klotho-derived peptide KP1 ameliorates SARS-CoV-2-associated acute kidney injury</strong> - Introduction: The severe cases of COVID-19, a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often present with acute kidney injury (AKI). Although old age and preexisting medical conditions have been identified as principal risk factors for COVID-19-associated AKI, the molecular basis behind such a connection remains unknown. In this study, we investigated the pathogenic role of Klotho deficiency in COVID-19-associated AKI and explored the therapeutic potential…</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>Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2</strong> - The coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (M^(pro)) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibiting enzyme inhibitory activity against M^(pro) (K(i): 1-10 μM) good anti-SARS-CoV-2 infection activity in the low micromolar range (EC(50): 1-12 μM) without significant toxicity. Additional kinetic studies of compounds FGA145,…</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>Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity</strong> - Due to the paucity of longitudinal molecular studies of COVID-19, particularly those covering the early stages of infection (Days 1-8 symptom onset), our understanding of host response over the disease course is limited. We perform longitudinal single cell RNA-seq on 286 blood samples from 108 age- and sex-matched COVID-19 patients, including 73 with early samples. We examine discrete cell subtypes and continuous cell states longitudinally, and we identify upregulation of type I IFN-stimulated…</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>Quantitative comparison of nuclear transport inhibition by SARS coronavirus ORF6 reveals the importance of oligomerization</strong> - Open Reading Frame 6 (ORF6) proteins, which are unique to severe acute respiratory syndrome-related (SARS) coronavirus, inhibit the classical nuclear import pathway to antagonize host antiviral responses. Several alternative models were proposed to explain the inhibitory function of ORF6 [H. Xia et al., Cell Rep. 33, 108234 (2020); L. Miorin et al., Proc. Natl. Acad. Sci. U.S.A. 117, 28344-28354 (2020); and M. Frieman et al., J. Virol. 81, 9812-9824 (2007)]. To distinguish these models and build…</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>NF9 peptide specific cytotoxic T lymphocyte clone cross react to Y453F mutation of SARS-CoV-2 virus spike protein</strong> - The recognition by cytotoxic T cells (CTLs) is essential for the clearance of SARS-CoV-2 virus-infected cells. Several viral proteins have been described to be recognized by CTLs. Among them, the spike (S) protein is one of the immunogenic proteins. The S protein acts as a ligand for its receptors, and several mutants with different affinities for its cognate receptors have been reported, and certain mutations in the S protein, such as L452R and Y453F, have been found to inhibit 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>T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID</strong> - CONCLUSIONS: Our observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID.</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>Antimicrobial and Antioxidant Properties of <em>Theobroma cacao</em>, <em>Bourreria huanita</em>, <em>Eriobotrya japonica</em>, and <em>Elettaria cardamomum</em> - Traditional Plants Used in Central America</strong> - The search for alternative naturally occurring antimicrobial agents will always continue, especially when emerging diseases like COVID-19 provide an urgency to identify and develop safe and effective ways to prevent or treat these infections. The purpose of this study was to evaluate the potential antimicrobial activity as well as antioxidant properties of commercial samples from four traditional medicinal plants used in Central America: Theobroma cacao, Bourreria huanita, Eriobotrya japonica,…</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>Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target</strong> - The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has made it clear that further development of antiviral therapies will be needed to combat additional SARS-CoV-2 variants or novel CoVs. Here, we describe small molecule inhibitors for SARS-CoV-2 Mac1, which counters ADP-ribosylation mediated innate immune responses. The compounds inhibiting Mac1 were discovered through high-throughput screening (HTS) using a protein FRET-based competition assay…</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 Antiviral Activity of a New Indol-3-carboxylic Acid Derivative Against SARS-CoV-2</strong> - The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are…</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>De-stabilizing innate immunity in COVID-19: effects of its own positive feedback and erratic viraemia on the alternative pathway of complement</strong> - Complement provides powerful, fast responses in the human circulation to SARS-CoV-2 (COVID-19 virus) infection of the lower respiratory tract. COVID-19 effects were investigated in a revised human in silico Mass Action model of complement’s alternative pathway (AP) responses. Bursts of newly circulating virions increased the fission of Complement protein C3 into C3a and C3b via stimulation of the lectin pathway or inhibited complement factor H. Viral reproduction sub-models incorporated smoothly…</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>Apolipoprotein C3 (ApoC3) facilitates NLRP3 mediated pyroptosis of macrophages through mitochondrial damage by accelerating of the interaction between SCIMP and SYK pathway in acute lung injury</strong> - Respiratory failure caused by severe acute lung injury (ALI) is the main cause of mortality in patients with COVID-19.This study aimed to investigate the effects and underlying biological mechanism of Apolipoprotein C3 (ApoC3) in ALI. To establish an in vivo model, C57BL/6 mice were exposed by lipopolysaccharide (LPS). For the in vitro model, murine bone marrow-derived macrophages (BMDMs) or RAW264.7 cells were stimulated with LPS + adenosine triphosphate (ATP). Serum levels of ApoC3 were found…</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>Peptidomimetics as potent dual SARS-CoV-2 cathepsin-L and main protease inhibitors: In silico design, synthesis and pharmacological characterization</strong> - In this paper we present the design, synthesis, and biological evaluation of a new series of peptidomimetics acting as potent anti-SARS-CoV-2 agents. Starting from our previously described Main Protease (M^(Pro)) and Papain Like Protease (PL^(Pro)) dual inhibitor, CV11, here we disclose its high inhibitory activity against cathepsin L (CTSL) (IC(50) = 19.80 ± 4.44 nM), an emerging target in SARS-CoV-2 infection machinery. An in silico design, inspired by the structure of CV11, led to the…</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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