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<title>14 November, 2023</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>Integrating stimulus-organism-response model and theory of planned behavior to explore athletes’ intention to receive the COVID-19 vaccine booster - A moderated mediation model</strong> -
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This study aims to investigate the factors influencing athletes9 intention to receive the COVID-19 vaccine booster in Mainland China by integrating the stimulus-organization-response (SOR) model and theory of planned behavior (TPB) as the theoretical framework. Purposive sampling was used to select respondents from the National Games of the People9s Republic of China. Hard-copy questionnaires were utilized to collect data, resulting in 981 valid responses. Descriptive analysis and partial least squares structural equation modeling were used to analyze the data. The findings reveal that athletes9 subjective norm and knowledge significantly influence attitude, commitment, and perceived behavioral control. Attitude, commitment, and perceived behavioral control are verified as full mediators between subjective norm, knowledge, and intention to receive the COVID-19 vaccine booster. Knowledge to commitment is the most powerful path to predict athletes9 intention to receive the COVID-19 vaccine booster. Motivation moderates the relationships between knowledge, attitude, commitment, and perceived behavioral control. The integrating model9s explanatory power is 83.2%. Athletes9 knowledge is crucial in shaping a positive attitude, commitment, and perceived control, enhancing their intention to get the COVID-19 vaccine booster.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.13.23298480v1" target="_blank">Integrating stimulus-organism-response model and theory of planned behavior to explore athletes’ intention to receive the COVID-19 vaccine booster - A moderated mediation model</a>
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</div></li>
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<li><strong>A SOLUTION TO THE KERMACK AND MCKENDRICK INTEGRO-DIFFERENTIAL EQUATIONS WHICH ACCURATELY PROJECTS COVID-19 CASE DATA USING GOOGLE MOBILITY DATA AS AN INPUT</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. We demonstrate the veracity of the KMES using the Google Residential Mobility Measure to accurately project case data from the Covid 19 pandemic and we derive many useful, but previously unknown, analytical expressions for characterizing and managing an epidemic. These include expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections. The KMES can also be cast in the form of a step function system response to the input of new infections; and that response is the time series of total infections. Since the publication of Kermack and McKendricks seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions 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 integro-differential equations, and that the approximation is a special case which adequately reproduces the dynamics of the integro-differential equations mapped onto the physical world. However, the KMES demonstrates that the SIR approximations are not adequate representations of the integro-differential equations, and we therefore suggest that the KMES obsoletes the need for the SIR approximations by providing not only a new mathematical perspective, but a new understanding of epidemic dynamics.
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</p>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.13.23298463v1" target="_blank">A SOLUTION TO THE KERMACK AND MCKENDRICK INTEGRO-DIFFERENTIAL EQUATIONS WHICH ACCURATELY PROJECTS COVID-19 CASE DATA USING GOOGLE MOBILITY DATA AS AN INPUT</a>
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<li><strong>Assessing the Impact of Mask Mandates on SARS-CoV-2 Transmission: A Case Study of Utah</strong> -
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Background: Throughout the COVID-19 pandemic, the effectiveness of face masks mandates has been intensely debated. Many methods have been used to demonstrate mask effectiveness, including one that compares the change in reproduction number following implementing and removing face mask mandates. Methods: Using data from Utah, we calculated the effect of mask mandates (E<sub>Fm</sub>) in each local health district from before and after three key mandates: the Salt Lake and Summit County (SLSC) mask mandates enacted; the Utah statewide mask mandate enacted; and the Utah statewide mandate was lifted. Results: We found that most counties had a reduction in the growth rate of cases following the mandates. There were reductions in E<sub>Fm</sub> in many counties after the introduction of the SLSC mask mandates and a more widespread reduction in E<sub>Fm</sub> across the state following the statewide mandate. Lifting the mandates, many counties across the states saw an increase in E<sub>Fm</sub>. Conclusion: Our data show mask mandates were an effective way to reduce transmission both within the jurisdiction they were enacted and in neighboring jurisdictions. We provide evidence to support mask mandates as a way to prevent transmission to be better equipped to respond to future pandemics.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.13.23298464v1" target="_blank">Assessing the Impact of Mask Mandates on SARS-CoV-2 Transmission: A Case Study of Utah</a>
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<li><strong>Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</strong> -
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The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to significant global morbidity and mortality. A crucial viral protein, the non-structural protein 14 (nsp14), catalyzes the methylation of viral RNA and plays a critical role in viral genome replication and transcription. Due to the low mutation rate in the nsp region among various SARS-CoV-2 variants, nsp14 has emerged as a promising therapeutic target. However, discovering potential inhibitors remains a challenge. In this work, we introduce a computational pipeline for the rapid and efficient identification of potential nsp14 inhibitors by leveraging virtual screening and the NCI open compound collection, which contains 250,000 freely available molecules for researchers worldwide. The introduced pipeline provides a cost-effective and efficient approach for early-stage drug discovery by allowing researchers to evaluate promising molecules without incurring synthesis expenses. Our pipeline successfully identified seven promising candidates after experimentally validating only 40 compounds. Notably, we discovered NSC620333, a compound that exhibits a strong binding affinity to nsp14 with a dissociation constant of 427 {+/-} 84 nM. In addition, we gained new insights into the structure and function of this protein through molecular dynamics simulations. We identified new conformational states of the protein and determined that residues Phe367, Tyr368, and Gln354 within the binding pocket serve as stabilizing residues for novel ligand interactions. We also found that metal coordination complexes are crucial for the overall function of the binding pocket. Lastly, we present the solved crystal structure of the nsp14-MTase complexed with SS148 (PDB:8BWU), a potent inhibitor of methyltransferase activity at the nanomolar level (IC50 value of 70 {+/-} 6 nM). Our computational pipeline accurately predicted the binding pose of SS148, demonstrating its effectiveness and potential in accelerating drug discovery efforts against SARS-CoV-2 and other emerging viruses.
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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/10.1101/2023.10.03.560722v2" target="_blank">Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors</a>
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</div></li>
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<li><strong>Real-world Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents</strong> -
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Background: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant9s emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. Objective: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. Design: Comparative effectiveness research accounting for underreported vaccination in three study cohorts: adolescents (12 to 20 years) during the Delta phase, children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. Setting: A national collaboration of pediatric health systems (PEDSnet). Participants: 77,392 adolescents (45,007 vaccinated) in the Delta phase, 111,539 children (50,398 vaccinated) and 56,080 adolescents (21,180 vaccinated) in the Omicron period. Exposures: First dose of the BNT162b2 vaccine vs. no receipt of COVID-19 vaccine. Measurements: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100% with confounders balanced via propensity score stratification. Results: During the Delta period, the estimated effectiveness of BNT162b2 vaccine was 98.4% (95% CI, 98.1 to 98.7) against documented infection among adolescents, with no significant waning after receipt of the first dose. An analysis of cardiac complications did not find an increased risk after vaccination. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (95% CI, 72.2 to 76.2). Higher levels of effectiveness were observed against moderate or severe COVID-19 (75.5%, 95% CI, 69.0 to 81.0) and ICU admission with COVID-19 (84.9%, 95% CI, 64.8 to 93.5). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (95% CI, 83.8 to 87.1), with 84.8% (95% CI, 77.3 to 89.9) against moderate or severe COVID-19, and 91.5% (95% CI, 69.5 to 97.6)) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined after 4 months following the first dose and then stabilized. The analysis revealed a lower risk of cardiac complications in the vaccinated group during the Omicron variant period. Limitations: Observational study design and potentially undocumented infection. Conclusions: Our study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.16.23291515v3" target="_blank">Real-world Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents</a>
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<li><strong>How well do surveys on adherence to pandemic policies assess actual behaviour: measurement properties of the Dutch Covid-19 Adherence to Prevention Advice Survey (CAPAS).</strong> -
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Background Survey data on adherence to COVID-19 prevention measures have often been used to inform policy makers and public health professionals. However, there is a lack of studies critically examining the validity and reliability of those self-reported measures. Aim We studied the measurement properties of the Covid-19 Adherence to Prevention Advice Survey (CAPAS), a novel questionnaire implemented in a repeated cross-sectional (i.e., ‘Trend’) Study and a Cohort Study in the Netherlands during the COVID-19 pandemic. Methods The CAPAS is a novel questionnaire developed in March 2020, with the aim to assess social activity and adherence to COVID-19 prevention measures. Items were formulated to minimise social desirability and aid memory retrieval. Based on the COSMIN framework, we investigated criterion validity by comparing trends of self-reported behaviour to trends in objective data. Responsiveness was assessed by studying whether self-reported behaviour changed following contextual (e.g., policy) changes. Test-retest reliability was examined over periods in which the context was stable. Results Overall, trends in self-reported behaviour closely corresponded to trends in external objective data. Self-reported behaviours were responsive to contextual changes and test-retest reliabilities were adequate. For infrequent behaviours reliability improved when measures were dichotomised. We were able to examine national representativeness for vaccination, which suggested a modest overestimation of on average 3.7%. Conclusions This study supports the suitability of using carefully designed, self-reported surveys (and the CAPAS specifically) to study changes in pandemic behaviours in a dynamic context.
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🖺 Full Text HTML: <a href="https://osf.io/rm8qn/" target="_blank">How well do surveys on adherence to pandemic policies assess actual behaviour: measurement properties of the Dutch Covid-19 Adherence to Prevention Advice Survey (CAPAS).</a>
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<li><strong>Tracking the development of COVID-19 related PsyArXiv preprints</strong> -
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Given the need for a rapid and critical response from behavioural sciences during times of crisis, this study investigated the trajectory of all preprints posted to the repository PsyArXiv up to 19 May 2020 that were related to COVID-19 (n = 211). Specifically, we examined the traction, impact, quality, and diversity of these preprints as compared to PsyArXiv preprints unrelated to COVID-19 (n = 167) and articles published in psychology journal articles (n = 75) within the same time frame. Preprints related to COVID-19 had similar traction to published journal articles on COVID-19, but compared to preprints unrelated to COVID-19, the COVID-19 preprints were more likely to be subsequently published during a follow-up period (until 2 March 2021), were published more quickly, and received more citations. Preprints related to COVID-19 reported fewer open science practices than preprints unrelated to COVID-19, but more than COVID-19 journal articles. Primary affiliations for all article types predominantly originated from Western countries, but this was comparatively more for preprints (both related to and not related to COVID-19), even though preprints had more international authorship teams than journal articles. Overall, the results demonstrate that some of the structural problems in research are still in play despite the global effort to mobilise research efforts during the pandemic.
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/evmgs/" target="_blank">Tracking the development of COVID-19 related PsyArXiv preprints</a>
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<li><strong>Basic Psychological Needs, Quality of Motivation, and Protective Behavior Intentions: A Nationally Representative Survey</strong> -
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This is a pre-print of a study published at Health Psychology and Behavioral Medicine https://doi.org/10.1080/21642850.2023.2257295. Objective: Citizens’ volitional engagement in protective behaviors is essential for successful pandemic management, as much of the required adherence is beyond authorities’ control and difficult to monitor. Building on the Self-Determination Theory (SDT), this study examines how basic psychological need satisfaction (BPNS) related to COVID-19 behavioral measures is associated with the quality of motivation (autonomous vs. controlled), and whether this quality of motivation is predictive of the intention to wear a face mask and to avoid meeting others. Methods: Cross-sectional survey study involving a nationally representative sample (N = 2272) was conducted in Finland in May 2021, when protective behaviors were recommended to prevent acceleration of the epidemic. Mann-Whitney U tests, Kruskal-Wallis tests, linear regression analysis, and multinomial logistic regression were conducted. Results: All three psychological needs were positively related to autonomous motivation (all p<.001). Satisfaction of autonomy (β = .234) and relatedness (β = .402) had larger effects than competence (β = .091). Autonomous motivation (range Exp(B) = 1.82‒3.55, p = .001) was consistently related to intention to wear a mask and intention to avoid meeting people. Controlled motivation (range Exp(B) = .66‒.93, p = .001‒.457) was associated with decreased protective behavior intentions. The effects of amotivation (range Exp(B) = .65‒1.02, p = .001‒.911) varied across analyses. Conclusions: Fostering autonomous motivation could increase adherence to protective behaviors in situations without clear mandates. The results also suggest that increasing perceptions of pressure or appealing to personal risk and fear may not advance adherence as effectively.
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🖺 Full Text HTML: <a href="https://osf.io/qgvua/" target="_blank">Basic Psychological Needs, Quality of Motivation, and Protective Behavior Intentions: A Nationally Representative Survey</a>
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<li><strong>Single Nucleus RNA Sequencing of Remnant Kidney Biopsies and Urine Cell RNA Sequencing Reveal Cell Specific Markers of Covid-19 Acute Kidney Injury</strong> -
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Acute kidney injury (AKI) in COVID-19 patients is associated with high mortality and morbidity. Critically ill COVID-19 patients are at twice the risk of in-hospital mortality compared to non-COVID AKI patients. We know little about the cell-specific mechanism in the kidney that contribute to worse clinical outcomes in these patients. New generation single cell technologies have the potential to provide insights into physiological states and molecular mechanisms in COVID-AKI. One of the key limitations is that these patients are severely ill posing significant risks in procuring additional biopsy tissue. We recently generated single nucleus RNA-sequencing data using COVID-AKI patient biopsy tissue as part of the human kidney atlas. Here we describe this approach in detail and report deeper comparative analysis of snRNAseq of 4 COVID-AKI, 4 reference, and 6 non-COVID-AKI biopsies. We also generated and analyzed urine transcriptomics data to find overlapping COVID-AKI-enriched genes and their corresponding cell types in the kidney from snRNA-seq data. We identified all major and minor cell types and states by using by using less than a few cubic millimeters of leftover tissue after pathological workup in our approach. Differential expression analysis of COVID-AKI biopsies showed pathways enriched in viral response, WNT signaling, kidney development, and cytokines in several nephron epithelial cells. COVID-AKI profiles showed a much higher proportion of altered TAL cells than non-COVID AKI and the reference samples. In addition to kidney injury and fibrosis markers indicating robust remodeling we found that, 17 genes overlap between urine cell COVID-AKI transcriptome and the snRNA-seq data from COVID-AKI biopsies. A key feature was that several of the distal nephron and collecting system cell types express these markers. Some of these markers have been previously observed in COVID-19 studies suggesting a common mechanism of injury and potentially the kidney as one of the sources of soluble factors with a potential role in disease progression.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.10.566497v1" target="_blank">Single Nucleus RNA Sequencing of Remnant Kidney Biopsies and Urine Cell RNA Sequencing Reveal Cell Specific Markers of Covid-19 Acute Kidney Injury</a>
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<li><strong>Recreating the Biological Steps of Viral Infection on a Bioelectronic Platform to Profile Viral Variants of Concern</strong> -
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Viral mutation rates frequently outpace the development of technologies used to detect and identify harmful variants; for SARS Coronavirus-2 (SARS-CoV-2), these are called variants of concern (VOC). Given the continual emergence of VOC, there is a critical need to develop platforms that can identify the presence of a virus and readily identify its propensity for infection. We present an electronic biomembrane sensing platform that recreates the multifaceted and sequential biological cues that give rise to distinct SARS-CoV-2 virus host cell entry pathways and reports the progression of entry steps of these pathways as electrical signals. Within these electrical signals, two necessary entry processes mediated by the viral Spike protein, virus binding and membrane fusion, can be distinguished. Remarkably, we find that closely related VOC exhibit distinct fusion signatures that correlate with trends reported in cell-based infectivity assays, allowing us to report quantitative differences in fusion characteristics among them that inform their infectivity potentials. This cell-free biomimetic infection platform also has a virus-free option that equally reports infectivity potential of the Spike proteins. We used SARS-CoV-2 as our prototype, but we anticipate that this platform will extend to other enveloped viruses and cell lines to quantifiably explore virus/host interactions. This advance should aid in faster determination of entry characteristics and fusogenicities of future VOC, necessary for rapid response.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.11.566634v1" target="_blank">Recreating the Biological Steps of Viral Infection on a Bioelectronic Platform to Profile Viral Variants of Concern</a>
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<li><strong>The SARS-CoV-2 Omicron sub-variant BA.2.86 is attenuated in hamsters</strong> -
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SARS-CoV-2 variants have emerged throughout the COVID-19 pandemic. There is a need to risk-assess newly emerged variants in near 'real-time' to estimate their potential threat to public health. The recently emerged Omicron sub-variant BA.2.86 raised concerns as it carries a high number of mutations compared to its predecessors. Here, we assessed the virulence of BA.2.86 in hamsters. We compared the pathogenesis of BA.2.86 and BA.2.75, as the latter is one of the most virulent Omicron sub-variants in this animal model. Using digital pathology pipelines, we quantified the extent of pulmonary lesions measuring T cell and macrophage infiltrates, in addition to alveolar epithelial hyperplasia. We also assessed body weight loss, clinical symptoms, virus load in oropharyngeal swabs, and virus replication in the respiratory tract. Our data show that BA.2.86 displays an attenuated phenotype in hamsters, suggesting that it poses no greater risk to public health than its parental Omicron sub-variants.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.10.566576v1" target="_blank">The SARS-CoV-2 Omicron sub-variant BA.2.86 is attenuated in hamsters</a>
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<li><strong>Insights into B Cell and Antibody Kinetics Against SARS-CoV-2 Variants Using Mathematical Modelling</strong> -
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B cells and antibodies are crucial in protecting against infections like SARS-CoV-2. However, antibody levels decline after infection or vaccination, reducing defences against future SARS-CoV-2 infections. To understand antibody production and decline, we developed a mathematical model that predicts germinal center B cell, long-lived plasma cell, memory B cell, and antibody dynamics. Our focus was on B cell activation and antibody generation following both primary and secondary SARS-CoV-2 infections. Aligning our model with clinical data, we adjusted antibody production rates for germinal center B cells and plasma B cells during primary and secondary infections. We also assessed antibody neutralization against Delta and Omicron variants post-primary and secondary exposure. Our findings showed reduced neutralization against Omicron due to its immune evasion. In primary and secondary exposures to Delta and Omicron, our predictions indicated enhanced antibody neutralization in the secondary response within a year of the primary response. We also explored waning immunity, demonstrating how B cell kinetics affect viral neutralization post-primary infection. This study enhances our understanding of humoral immunity to SARS-CoV-2 and can predict antibody dynamics post-infection or vaccination.
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.11.10.566587v1" target="_blank">Insights into B Cell and Antibody Kinetics Against SARS-CoV-2 Variants Using Mathematical Modelling</a>
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<li><strong>Crykey: Rapid Identification of SARS-CoV-2 Cryptic Mutations in Wastewater</strong> -
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We present Crykey, a computational tool for rapidly identifying cryptic mutations of SARS-CoV-2. Specifically, we identify co-occurring single nucleotide mutations on the same sequencing read, called linked-read mutations, that are rare or entirely missing in existing databases, and have the potential to represent novel cryptic lineages found in wastewater. While previous approaches exist for identifying cryptic linked-read mutations from specific regions of the SARS-CoV-2 genome, there is a need for computational tools capable of efficiently tracking cryptic mutations across the entire genome and for tens of thousands of samples and with increased scrutiny, given their potential to represent either artifacts or hidden SARS-CoV-2 lineages. Crykey fills this gap by identifying rare linked-read mutations that pass stringent computational filters to limit the potential for artifacts. We evaluate the utility of Crykey on >3,000 wastewater and >22,000 clinical samples; our findings are three-fold: i) we identify hundreds of cryptic mutations that cover the entire SARS-CoV-2 genome, ii) we track the presence of these cryptic mutations across multiple wastewater treatment plants and over a three years of sampling in Houston, and iii) we find a handful of cryptic mutations in wastewater mirror cryptic mutations in clinical samples and investigate their potential to represent real cryptic lineages. In summary, Crykey enables large-scale detection of cryptic mutations representing potential cryptic lineages in wastewater.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.06.16.23291524v2" target="_blank">Crykey: Rapid Identification of SARS-CoV-2 Cryptic Mutations in Wastewater</a>
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<li><strong>Application of the Fluctuation Test to the data of Morbidity and Mortality by COVID-19 in China 2020-2023</strong> -
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In this work the Luria and Delbruck Fluctuation Test was applied to the data of Morbidity and Mortality by COVID-19 in China from January 2020 to August 2023. Three types of data were used: es.statista.com, datosmacro.expansion.com and larepublica.co without modification, but trying to avoid and justify the anomalies and inconsistencies observed. The methods originally used to establish the interactions of two populations were evaluated: the viral population with that of its host and the drift of both organisms. Only the fluctuations of the weekly Variance of daily increase of Cases (Morbidity) and of the weekly Variance of daily increase of Deaths (Mortality) were studied. The results showed that the Fluctuation Test is applicable to the selected data from China and other data from India, Japan and South Korea, used as controls. The study was separated into two periods: a first initial period from January 2020 to September 2021 and a second final period from October 2021 to August 2023. Results were obtained for Morbidity and Mortality that relate the fluctuations of the first with the fluctuations of the second. However, it was possible to detect some anomalies and uncertainties that were possibly derived from inconsistencies in the original data. A repeated fluctuation was observed in the boreal winter in January, February and March of each one of the year studied. A clear decrease in fluctuation was detected in that period in 2021 that could be attributed to the strict confinement during the quarantine in China between 2020 and 2021. Massive, extensive and intensive vaccinations failed to completely eliminate the most important fluctuations. In this work we tried to correlate the appearance of some virus variants with the fluctuations. The most relevant results of said correlation are presented. With the results of this work, the animal origin cannot be confirmed nor can the human or laboratory origin of the SARS CoV-2 virus that caused the initial emerging infection, be ruled out. However, it was concluded that this method could be used to search for clues about its origin. One of these keys is the comparison of the result of the first important fluctuation in the boreal winter of 2020 in each of the countries studied as controls: India, Japan and South Korea. The comparison of this result with the first fluctuation of China for that same period could give clues about the origin of the virus.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.12.23298174v1" target="_blank">Application of the Fluctuation Test to the data of Morbidity and Mortality by COVID-19 in China 2020-2023</a>
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<li><strong>Synergistic Role of NK Cells and Monocytes in Promoting Atherogenesis in Severe COVID-19 Patients.</strong> -
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Clinical data demonstrate an increased predisposition to cardiovascular disease (CVD) following severe COVID-19 infection. This may be driven by a dysregulated immune response associated with severe disease. Monocytes and vascular tissue resident macrophages play a critical role in atherosclerosis, the main pathology leading to ischemic CVD. Natural killer (NK) cells are a heterogenous group of cells that are critical during viral pathogenesis and are known to be dysregulated during severe COVID-19 infection. Their role in atherosclerotic cardiovascular disease has recently been described. However, the contribution of their altered phenotypes to atherogenesis following severe COVID-19 infection is unknown. We demonstrate for the first time that during and after severe COVID-19, circulating proinflammatory monocytes and activated NK cells act synergistically to increase uptake of oxidized low-density lipoprotein (Ox-LDL) into vascular tissue with subsequent foam cell generation leading to atherogenesis despite recovery from acute infection. Our data provide new insights, revealing the roles of monocytes/macrophages, and NK cells in COVID-19-related atherogenesis.
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🖺 Full Text HTML: <a href="https://www.medrxiv.org/content/10.1101/2023.11.10.23298322v1" target="_blank">Synergistic Role of NK Cells and Monocytes in Promoting Atherogenesis in Severe COVID-19 Patients.</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>A Multicenter, Adaptive, Randomized, doublE-blinded, Placebo-controlled Study in Participants With Long COVID-19: The REVIVE Trial</strong> - <b>Conditions</b>: Long COVID-19 Syndrome; Chronic Fatigue Syndrome <br/><b>Interventions</b>: Drug: Fluvoxamine Maleate 100 MG; Drug: Placebo; Drug: Metformin Extended Release Oral Tablet <br/><b>Sponsors</b>: Cardresearch <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>Connecting Friends and Health Workers to Boost COVID-19 Vaccination in Latino Communities</strong> - <b>Conditions</b>: COVID-19 Vaccine Uptake <br/><b>Interventions</b>: Behavioral: REDES; Behavioral: Control <br/><b>Sponsors</b>: Johns Hopkins University; National Institute on Minority Health and Health Disparities (NIMHD); Rutgers University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Influence of Hypoxic, Normobaric and Hypobaric Training on the Immunometabolism of Post-covid-19 Athletes</strong> - <b>Conditions</b>: Normobaric Hypoxia; Hypoventilation; Normoxia <br/><b>Interventions</b>: Other: Repeated sprint <br/><b>Sponsors</b>: Faculdade de Motricidade Humana; University of Sao Paulo; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ <br/><b>Sponsors</b>: Abbott Rapid Dx <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>The Safety and Tolerability of A8G6 COVID-19 Neutralization Antibody Combined With Nasal Spray</strong> - <b>Conditions</b>: SARS-CoV-2; Prevention <br/><b>Interventions</b>: Biological: A8G6 SARS-CoV-2 Neutralization Antibody combination nasal spray; Other: A8G6 SARS-CoV-2 Neutralization Antibody nasal excipient <br/><b>Sponsors</b>: The Second Affiliated Hospital of Chongqing Medical University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Building Engagement Using Financial Incentives Trial - Colorectal Cancer Screening</strong> - <b>Conditions</b>: Health Behavior; Colorectal Cancer; Influenza; COVID-19; Vaccine Hesitancy; Vaccine-Preventable Diseases; Healthcare Patient Acceptance <br/><b>Interventions</b>: Behavioral: Financial incentive for colorectal cancer screening; Behavioral: Financial incentive for flu shot; Behavioral: Financial incentive for COVID-19 shot <br/><b>Sponsors</b>: Tulane University; National Heart, Lung, and Blood Institute (NHLBI) <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>Clinical Evaluation of the Panbio™ COVID-19/Flu A&B Panel to Support Home Use</strong> - <b>Conditions</b>: COVID-19; Influenza A; Influenza Type B <br/><b>Interventions</b>: Diagnostic Test: Panbio™ COVID-19/Flu A&B Panel <br/><b>Sponsors</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>Effects of Rehabilitation Combined With a Maintenance Program Compared to Rehabilitation Alone in Post-COVID-19</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome <br/><b>Interventions</b>: Procedure: Rehabilitation combined to a digital maintenance program; Procedure: Rehabilitation only <br/><b>Sponsors</b>: Schön Klinik Berchtesgadener Land; Bavarian State Ministry of Health and Care (Funding); Deutsche Rentenversicherung Bund (German pension insurance) (Design); Betriebskrankenkassen Landesverband Bayern (Bavarian health insurance) (Design) <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>Child and Adolescent Mental Health Literacy for Primary Schools Teachers. A Multicomponent Intervention</strong> - <b>Conditions</b>: Child Mental Health <br/><b>Interventions</b>: Behavioral: Child Mental Health Literacy Program <br/><b>Sponsors</b>: Universidad de Valparaiso <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>Brief Digital Intervention to Increase COVID-19 Vaccination Among Individuals With Anxiety or Depression</strong> - <b>Conditions</b>: Misinformation; Vaccine Hesitancy; Anxiety; Depression; COVID-19 <br/><b>Interventions</b>: Behavioral: Attitudinal inoculation; Behavioral: Cognitive-behavioral therapy-informed intervention; Behavioral: Conventional public health messaging <br/><b>Sponsors</b>: City University of New York, School of Public Health; University of North Carolina, Chapel Hill <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 PhaseⅡ Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 mRNA Vaccine (ZSVG-02-O); Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) 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>Pilot Randomized Study of RD-X19 Tx Device in Subjects With PCC (Long Covid) in the Outpatient Setting</strong> - <b>Conditions</b>: Post COVID-19 Condition (PCC) <br/><b>Interventions</b>: Device: RDX-19 <br/><b>Sponsors</b>: KNOWBio Inc.; NAMSA <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>CPAP Therapy Through a Helmet or a Full Face Mask in Patients With Acute Hypoxemic Respiratory Failure: Cross-over Study</strong> - <b>Conditions</b>: Pneumonia, Bacterial; Respiratory Failure; COVID-19 Pneumonia <br/><b>Interventions</b>: Diagnostic Test: Arterial blood gases; Diagnostic Test: Respiratory rate (RR); Diagnostic Test: Pulseoximeter; Diagnostic Test: Assessment of accessory respiratory muscles work; Diagnostic Test: Esophageal pressure measurement; Diagnostic Test: Discomfort Visual Analog Scale (VAS); Diagnostic Test: Noninvasive blood pressure; Diagnostic Test: Heart rate <br/><b>Sponsors</b>: I.M. Sechenov First Moscow State Medical University <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Investigation of Efficacy and Safety of Electrical Signal Therapy Provided by Dr Biolyse® Device in COVID-19 Disease</strong> - <b>Conditions</b>: COVID-19 Pneumonia; Virus Diseases; COVID-19 <br/><b>Interventions</b>: Device: Signal Therapy provided by Dr.Biolyse device; Other: Liquid Support Treatment <br/><b>Sponsors</b>: AVB Biotechnology <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Phase 1 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine</strong> - <b>Conditions</b>: SARS-CoV-2 Infection <br/><b>Interventions</b>: Biological: Placebo; Biological: COVID-19 Vaccine (Vero Cell) ,Inactivated; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 10 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 30 μg; Biological: COVID-19 mRNA Vaccine (ZSVG-02-O) 60 μg <br/><b>Sponsors</b>: CNBG-Virogin Biotech (Shanghai) Ltd.; Shulan (Hangzhou) Hospital <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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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Intranasal G5-BGG/pDNA vaccine elicits protective systemic and mucosal immunity against SARS-CoV-2 by transfecting mucosal dendritic cells</strong> - Infectious disease pandemics, including the coronavirus disease 2019 pandemic, have heightened the demand for vaccines that provide both disease protection and transmission inhibition. Although parenteral vaccines induce robust systemic immunity, their effectiveness in respiratory mucosae is limited. Considering the crucial role of nasal-associated lymphoid tissue (NALT) in mucosal immune responses, in this study, the intranasal complex composed of G5-BGG and antigen-expressing plasmid DNA…</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>Colloidal aggregation confounds cell-based Covid-19 antiviral screens</strong> - Colloidal aggregation is one of the largest contributors to false-positives in early drug discovery and chemical biology. Much work has focused on its impact on pure-protein screens; here we consider aggregations role in cell-based infectivity assays in Covid-19 drug repurposing. We began by investigating the potential aggregation of 41 drug candidates reported as SARs-CoV-2 entry inhibitors. Of these, 17 formed colloidal-particles by dynamic light scattering and exhibited detergent-dependent…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Application of Luteolin in Neoplasms and Nonneoplastic Diseases</strong> - Researchers are amazed at the multitude of biological effects of 3’,4’,5,7-tetrahydroxyflavone, more commonly known as luteolin, as it simultaneously has antioxidant and pro-oxidant, as well as antimicrobial, anti-inflammatory, and cancer-preventive, properties. The anticancer properties of luteolin constitute a mosaic of pathways due to which this flavonoid influences cancer cells. Not only is it able to induce apoptosis and inhibit cancer cell proliferation, but it also suppresses angiogenesis…</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>HSP90AB1 Is a Host Factor Required for Transmissible Gastroenteritis Virus Infection</strong> - Transmissible gastroenteritis virus (TGEV) is an important swine enteric coronavirus causing viral diarrhea in pigs of all ages. Currently, the development of antiviral agents targeting host proteins to combat viral infection has received great attention. The heat shock protein 90 (HSP90) is a critical host factor and has important regulatory effects on the infection of various viruses. However, its roles in porcine coronavirus infection remain unclear. In this study, the effect of HSP90 on TGEV…</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>Therapeutic Effect and Safety Evaluation of Naringin on <em>Klebsiella pneumoniae</em> in Mice</strong> - Critically ill patients with Corona Virus Disease 2019 (COVID-19) often develop secondary bacterial infections that pose a significant threat to patient life safety, making the development of drugs to prevent bacterial infections in the lungs critical to clinical care. Naringin (NAR) is one of the significant natural flavonoids rich in Pummelo Peel (Hua Ju Hong), with anti-inflammatory, antimicrobial, and antioxidant activities, and is commonly used in treating respiratory tract infectious…</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>Interaction of Methylene Blue with Severe Acute Respiratory Syndrome Coronavirus 2 Envelope Revealed by Molecular Modeling</strong> - Methylene blue has multiple antiviral properties against Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2). The ability of methylene blue to inhibit different stages of the virus life cycle, both in light-independent and photodynamic processes, is used in clinical practice. At the same time, the molecular aspects of the interactions of methylene blue with molecular components of coronaviruses are not fully understood. Here, we use Brownian dynamics to identify methylene blue…</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>Genetic Predisposition to Elevated Levels of Circulating ADAM17 Is Associated with the Risk of Severe COVID-19</strong> - High levels of ADAM17 activity have emerged as an important mediator in severe COVID-19. This study aims to characterize eventual causal relationships between ADAM17 and COVID-19. Using Mendelian randomization analyses, we examined the causal effects of circulating ADAM17 on COVID-19 outcomes using summary statistics from large, genome-wide association studies of ADAM17 (up to 35,559 individuals) from the Icelandic Cancer Project and deCODE genetics, as well as critically ill COVID-19 patients…</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>Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics</strong> - The emergence of lethal coronaviruses follows a periodic pattern which suggests a recurring cycle of outbreaks. It remains uncertain as to when the next lethal coronavirus will emerge, though its eventual emergence appears to be inevitable. New mutations in evolving SARS-CoV-2 variants have provided resistance to current antiviral drugs, monoclonal antibodies, and vaccines, reducing their therapeutic efficacy. This underscores the urgent need to investigate alternative therapeutic approaches….</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>Novel Substituted Azoloazines with Anticoagulant Activity</strong> - Hypercytokinemia, or cytokine storm, often complicates the treatment of viral and bacterial infections, including COVID-19, leading to the risk of thrombosis. However, the use of currently available direct anticoagulants for the treatment of COVID-19 patients is limited due to safety reasons. Therefore, the development of new anticoagulants remains an urgent task for organic and medicinal chemistry. At the same time, new drugs that combine anticoagulant properties with antiviral or antidiabetic…</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>Insights into the mechanism of SARS-CoV-2 main protease autocatalytic maturation from model precursors</strong> - A critical step for SARS-CoV-2 assembly and maturation involves the autoactivation of the main protease (MPro^(WT)) from precursor polyproteins. Upon expression, a model precursor of MPro^(WT) mediates its own release at its termini rapidly to yield a mature dimer. A construct with an E290A mutation within MPro exhibits time dependent autoprocessing of the accumulated precursor at the N-terminal nsp4/nsp5 site followed by the C-terminal nsp5/nsp6 cleavage. In contrast, a precursor containing…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Safety and immunogenicity of the third and fourth doses of vaccine against SARS-CoV-2 following a 2-dose regimen of inactivated whole-virion SARS-CoV-2 vaccine</strong> - This study followed healthcare personnel (HCP) who had completed a primary series of CoronaVac and then received the third and fourth doses of COVID-19 vaccine. The primary objective was to determine the seroconversion rate of neutralizing antibodies against wild-type SARS-CoV-2 and VOCs at day 28 after the third dose of vaccine and day 28 after the fourth dose of vaccine. This prospective cohort study was conducted at Maharaj Nakorn Chiang Mai Hospital, a tertiary care hospital affiliated 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>Mechanistic and thermodynamic characterization of antiviral inhibitors targeting nucleocapsid N-terminal domain of SARS-CoV-2</strong> - The nucleocapsid (N) protein of SARS-CoV-2 plays a pivotal role in encapsulating the viral genome. Developing antiviral treatments for SARS-CoV-2 is imperative due to the diminishing immunity of the available vaccines. This study targets the RNA-binding site located in the N-terminal domain (NTD) of the N-protein to identify the potential antiviral molecules against SARS-CoV-2. A structure-based repurposing approach identified the twelve high-affinity molecules from FDA-approved drugs, natural…</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>Exploring the disruption of SARS-CoV-2 RBD binding to hACE2</strong> - The COVID-19 pandemic was declared due to the spread of the novel coronavirus, SARS-CoV-2. Viral infection is caused by the interaction between the SARS-CoV-2 receptor binding domain (RBD) and the human ACE2 receptor (hACE2). Previous computational studies have identified repurposed small molecules that target the RBD, but very few have screened drugs in the RBD-hACE2 interface. When studies focus solely on the binding affinity between the drug and the RBD, they ignore the effect of hACE2,…</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>Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-<em>κ</em>B signaling cascade and inhibiting NLRP3 inflammasome activation</strong> - Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated…</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 review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19</strong> - Gastrodin is an extract from the dried tuber of the Chinese herb Gastrodia elata (Tian ma), with anti-inflammatory, antioxidant, and antiviral properties. Recent studies have shown that, compared to commonly used diabetes drugs, gastrodin has antidiabetic effects in multiple ways, with characteristics of low cost, high safety, less side effects, protection of β-cell function, relieving insulin resistance and alleviating multiple complications. In addition, it is confirmed that gastrodin can…</p></li>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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