172 lines
46 KiB
HTML
172 lines
46 KiB
HTML
|
<!DOCTYPE html>
|
|||
|
|
<html lang="" xml:lang="" xmlns="http://www.w3.org/1999/xhtml"><head>
|
|||
|
|
<meta charset="utf-8"/>
|
|||
|
|
<meta content="pandoc" name="generator"/>
|
|||
|
|
<meta content="width=device-width, initial-scale=1.0, user-scalable=yes" name="viewport"/>
|
|||
|
|
<title>13 March, 2024</title>
|
|||
|
|
<style>
|
|||
|
|
code{white-space: pre-wrap;}
|
|||
|
|
span.smallcaps{font-variant: small-caps;}
|
|||
|
|
span.underline{text-decoration: underline;}
|
|||
|
|
div.column{display: inline-block; vertical-align: top; width: 50%;}
|
|||
|
|
div.hanging-indent{margin-left: 1.5em; text-indent: -1.5em;}
|
|||
|
|
ul.task-list{list-style: none;}
|
|||
|
|
</style>
|
|||
|
|
<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
|
|||
|
|
<body>
|
|||
|
|
<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
|
|||
|
|
<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><a href="#from-preprints">From Preprints</a></li>
|
|||
|
|
<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
|
|||
|
|
<li><a href="#from-pubmed">From PubMed</a></li>
|
|||
|
|
<li><a href="#from-patent-search">From Patent Search</a></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li><strong>Mutational Profiling of SARS-CoV-2 PLpro in human cells reveals requirements for function, structure, and drug escape</strong> -
|
|||
|
|
<div>
|
|||
|
|
SARS-CoV-2, the causative agent of COVID-19, is responsible for the recent global pandemic and remains a major source of mortality. Papain-like protease (PLpro) is a target for SARS-CoV-2 inhibitor development, as it is not only essential for viral replication through cleavage of the viral poly-proteins pp1a and pp1ab, but also has de-ubiquitylation and de-ISGylation activities, which can affect innate immune responses. To understand the features of PLpro that dictate activity and anticipate how emerging PLpro variants will affect function, we employed Deep Mutational Scanning to evaluate the mutational effects on enzymatic activity and protein stability in mammalian cells. We confirm features of the active site and identify all mutations in neighboring residues that support or ablate activity. We characterize residues responsible for substrate binding and demonstrate that although the blocking loop is remarkably tolerant to nearly all mutations, its flexibility is important for enzymatic function. We additionally find a connected network of mutations affecting function but not structure that extends far from the active site. Using our DMS libraries we were able to identify drug-escape variants to a common PLpro inhibitor scaffold and predict that plasticity in both the S4 pocket and blocking loop sequence should be considered during the drug design process.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.11.584210v1" target="_blank">Mutational Profiling of SARS-CoV-2 PLpro in human cells reveals requirements for function, structure, and drug escape</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition</strong> -
|
|||
|
|
<div>
|
|||
|
|
A recombinant lineage of the SARS-CoV-2 Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for their improved immune evasion and transmissibility. Here, we determine cryo-EM structures of XBB.1.5, XBB.1.16, EG.5 and EG.5.1 spike (S) ectodomains to reveal reinforced 3-RBD-down receptor inaccessible closed states mediated by interprotomer receptor binding domain (RBD) interactions previously observed in BA.1 and BA.2. Improved XBB.1.5 and XBB.1.16 RBD stability compensated for stability loss caused by early Omicron mutations, while the F456L substitution reduced EG.5 RBD stability. S1 subunit mutations had long-range impacts on conformation and epitope presentation in the S2 subunit. Our results reveal continued S protein evolution via simultaneous optimization of multiple parameters including stability, receptor binding and immune evasion, and the dramatic effects of relatively few residue substitutions in altering the S protein conformational landscape.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.12.580004v2" target="_blank">SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Postnatal depression symptom trajectories across the COVID-19 pandemic: Evidence from the United Kingdom</strong> -
|
|||
|
|
<div>
|
|||
|
|
Purpose: Postnatal maternal mental health suffered early in the COVID-19 pandemic; here we explore the continuing trajectory of postnatal depressive symptoms in the UK. Methods: We report descriptive statistics from a six-wave longitudinal online survey, tracking a cohort of 569 mothers giving birth between November 2019 and December 2020, and a subsequent cohort of 70 mothers giving birth in 2022. Results: The percentage of participants meeting the ≥11 Edinburgh Postnatal Depression Scale cut-off for postnatal depression was high early in the pandemic; while declining as social distancing restrictions eased, rates remained above pre-pandemic levels in April 2022: 47.5% (May-June 2020), 32.8% (July 2020), 51.3% (late 2020), 54.0% (February 2021), 38.2% (September 2021), 35.1% (April 2022). Those with greater symptom severity early in the pandemic showed a tendency to remain in depressive range. Symptoms were higher, and the decline in symptoms overtime attenuated, in those experiencing financial difficulty. Of mothers giving birth in 2022, 44.3% scored ≥11. Conclusions: Health services must be alert to high support needs of this cohort in which postnatal depression appears chronic at high rates, particularly in those of lower socioeconomic position.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/8azct/" target="_blank">Postnatal depression symptom trajectories across the COVID-19 pandemic: Evidence from the United Kingdom</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation</strong> -
|
|||
|
|
<div>
|
|||
|
|
The evolution of SARS-CoV-2 variants and their respective phenotypes represents an important set of tools to understand basic coronavirus biology as well as the public health implications of individual mutations in variants of concern. While mutations outside of Spike are not well studied, the entire viral genome is undergoing evolutionary selection, particularly the central disordered linker region of the nucleocapsid (N) protein. Here, we identify a mutation (G215C), characteristic of the Delta variant, that introduces a novel cysteine into this linker domain, which results in the formation of a disulfide bond and a stable N-N dimer. Using reverse genetics, we determined that this cysteine residue is necessary and sufficient for stable dimer formation in a WA1 SARS-CoV-2 background, where it results in significantly increased viral growth both in vitro and in vivo. Finally, we demonstrate that the N:G215C virus packages more nucleocapsid per virion and that individual virions are larger, with elongated morphologies.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.08.584120v1" target="_blank">Variant mutation in SARS-CoV-2 nucleocapsid enhances viral infection via altered genomic encapsidation</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>SARS-CoV-2 Omicron BA.2.87.1 Exhibits Higher Susceptibility to Serum Neutralization Than EG.5.1 and JN.1</strong> -
|
|||
|
|
<div>
|
|||
|
|
As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions ({Delta}15-26 and {Delta}136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.10.584306v1" target="_blank">SARS-CoV-2 Omicron BA.2.87.1 Exhibits Higher Susceptibility to Serum Neutralization Than EG.5.1 and JN.1</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Community structure and temporal dynamics of SARS-CoV-2 epistatic network allow for early detection of emerging variants with altered phenotypes</strong> -
|
|||
|
|
<div>
|
|||
|
|
The emergence of viral variants with altered phenotypes is a public health challenge underscoring the need for advanced evolutionary forecasting methods. Given extensive epistatic interactions within viral genomes and known viral evolutionary history, efficient genomic surveillance necessitates early detection of emerging viral haplotypes rather than commonly targeted single mutations. Haplotype inference, however, is a significantly more challenging problem precluding the use of traditional approaches. Here, using SARS-CoV-2 evolutionary dynamics as a case study, we show that emerging haplotypes with altered transmissibility can be linked to dense communities in coordinated substitution networks, which become discernible significantly earlier than the haplotypes become prevalent. From these insights, we develop a computational framework for inference of viral variants and validate it by successful early detection of known SARS-CoV-2 strains. Our methodology offers greater scalability than phylogenetic lineage tracing and can be applied to any rapidly evolving pathogen with adequate genomic surveillance data.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.04.02.535277v2" target="_blank">Community structure and temporal dynamics of SARS-CoV-2 epistatic network allow for early detection of emerging variants with altered phenotypes</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Zheln.com: A protocol for a universal living overview of health-related systematic reviews</strong> -
|
|||
|
|
<div>
|
|||
|
|
BACKGROUND Objectives. 1. Identify and monitor most of published systematic reviews. 2. Tag the identified systematic records with medical specialties. 3. Select or crowdfund reviews for further appraisal. 4. Critically appraise and replicate the selected systematic reviews. 5. Disseminate practice implications of positively appraised reviews to both the public and evidence-based practitioners in health care and other fields associated with intervention into a human life, such as education, business, policy, or ecology. METHODS Eligibility criteria. Record eligibility is assessed by checking the record title and, if the title failed, abstract against the ‘true positive criteria’ for systematic reviews taken from the publication by Shojania & Bero, 2001 (PMID 11525102). The record/study flow is as follows: All eligible records are amenable for tagging, selection, and crowdfunding process; Only those eligible records that have been selected or crowdfunded are subject to critical appraisal; For all records that have been selected, all relevant reports are collected; Reports are grouped into studies; Only for the studies appraised positively, practical implications are summarized and disseminated. COVID-19 publications are not selected. Crowdfunding an appraisal of any eligible record is possible for any individual or organization. Information sources. MEDLINE via PubMed. Adding other search sources, such as Scopus, OSF, and medRxiv, is planned in the future when more appraisers become available. The Replicated Version of the PubMed Systematic Review Subset Query Zheln Edition (DOI 10.17605/OSF.IO/Z3JU7) will be used. The searches are run daily. Risk of bias. Critical appraisal will feature: Duplication assessment; Replication; Assessment against the MECIR conduct standards; ROB-ME assessment; GRADE assessment. Synthesis of results. No across-studies synthesis is planned. Within-studies, I will formulate explicit practice-relevant statements based on the extracted health outcomes and quality-of-conduct assessment. Also, the process of each critical appraisal is video-recorded and published on YouTube daily. OTHER Funding. The review is crowdfunded; the details are available from the Zheln website (https://zheln.com). Crowd funders had no role in the design of the protocol. They will be able to request critical appraisal and additional critical appraisal (with new data provided) of any eligible record but will not influence the review process otherwise. Registration. The project is hosted on GitHub. Also, there is an umbrella Open Science Framework project that links repositories and preprints (DOI 10.17605/OSF.IO/EJKFC). The protocol for this overview of systematic reviews has been submitted for registration in PROSPERO.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/preprints/metaarxiv/y2nrb/" target="_blank">Zheln.com: A protocol for a universal living overview of health-related systematic reviews</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion</strong> -
|
|||
|
|
<div>
|
|||
|
|
The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly. BA.2.87.1 is more resistant to neutralization by XBB.15-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.11.583978v1" target="_blank">Distinct Patterns of SARS-CoV-2 BA.2.87.1 and JN.1 Variants in Immune Evasion, Antigenicity and Cell-Cell Fusion</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Exploring the therapeutic potential of defective interfering particles in reducing the replication of SARS-CoV-2</strong> -
|
|||
|
|
<div>
|
|||
|
|
SARS-CoV-2 still presents a global threat to human health due to the continued emergence of new strains and waning immunity amongst vaccinated populations. Therefore, it is still relevant to investigate potential therapeutics, such as therapeutic interfering particles (TIPs). Mathematical and computational modelling are valuable tools to study viral infection dynamics for predictive analysis. Here, we expand on the previous work by Grebennikov et al. (2021) on SARS-CoV-2 intra-cellular replication dynamics to include defective interfering particles (DIPs) as potential therapeutic agents. We formulate a deterministic model that describes the replication of wild-type (WT) SARS-CoV-2 virus in the presence of DIPs. Sensitivity analysis of parameters to several model outputs is employed to inform us on those parameters to be carefully calibrated from experimental data. We then study the effects of co-infection on WT replication and how DIP dose perturbs the release of WT viral particles. Furthermore, we provide a stochastic formulation of the model that is compared to the deterministic one. These models could be further developed into population-level models or used to guide the development and dose of TIPs.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.11.584367v1" target="_blank">Exploring the therapeutic potential of defective interfering particles in reducing the replication of SARS-CoV-2</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Assessment for the seasonality of Covid-19 should focus on ultraviolet radiation and not ‘warmer days’</strong> -
|
|||
|
|
<div>
|
|||
|
|
More attention should be paid to ultraviolet radiation for the seasonality of Covid-19, based on the previous SARS and MERS epidemics, and not the ‘warmer days’ of summer.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://osf.io/397yg/" target="_blank">Assessment for the seasonality of Covid-19 should focus on ultraviolet radiation and not ‘warmer days’</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Protein complex heterogeneity and topology revealed by electron capture charge reduction and surface induced dissociation</strong> -
|
|||
|
|
<div>
|
|||
|
|
Herein, we focus on native mass spectrometry (nMS) combined with a fast, tunable gas-phase charge reduction, electron capture charge reduction (ECCR), and illustrate its utility in the characterization of protein complex topology and glycoprotein heterogeneity. ECCR is illustrated to effectively spread the charge states of tetradecameric GroEL, illustrating Orbitrap m/z measurement out to greater than 100,000 m/z. For both the pentameric C-reactive protein and tetradecameric GroEL, our novel device combining ECCR with surface induced dissociation (SID) lowers the charge states and produces more topologically informative fragmentation. While more native-like fragmentation has previously been illustrated for complexes charge reduced by proton abstraction in solution, this is the first illustration that ECCR can lead to more native-like SID fragmentation of protein complexes. Application to protein glycosylation, one of the most common and diverse protein posttranslational modifications, is also illustrated because glycosylation is important for structural and functional properties and plays essential roles in many key biological processes. The immense heterogeneity resulting from variability in glycosylation sites and glycan composition and structure poses significant analytical challenges that hinder a mechanistic understanding of the biological role of glycosylation. Data for stabilized heavily glycosylated SARS-CoV-2 spike protein trimer and thyroglobulin dimer illustrate that ECCR enables significantly improved resolution of glycan heterogeneity. Without ECCR, the charge states of a glycoprotein complex are not resolved and average mass determination is available only through the use of charge detection mass spectrometry or mass photometry. With ECCR after narrow m/z selection, multiple glycoform m/z values are apparent, providing quick global, glycoform profiling and providing a future path for glycan localization on individual intact glycoforms (e.g., though top-down dissociation).
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.07.583498v1" target="_blank">Protein complex heterogeneity and topology revealed by electron capture charge reduction and surface induced dissociation</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>In silico genomic surveillance by CoVerage predicts and characterizes SARS-CoV-2 Variants of Interest</strong> -
|
|||
|
|
<div>
|
|||
|
|
Rapidly evolving viral pathogens such as SARS-CoV-2 continuously accumulate amino acid changes, some of which affect transmissibility, virulence or improve the virus' ability to escape host immunity. Since the beginning of the pandemic and establishment of SARS-CoV-2 as a human pathogen, multiple lineages with concerning phenotypic alterations, so called Variants of Concern (VOCs), have emerged and risen to predominance. To optimize public health management and to ensure the continued efficacy of vaccines, the early detection of such variants of interest is essential. Therefore, large-scale viral genomic surveillance programs have been initiated worldwide, with data being deposited in public repositories in a timely manner. However, technologies for their continuous interpretation are currently lacking. Here, we describe the CoVerage system (www.sarscoverage.org) for viral genomic surveillance, which continuously predicts and characterizes novel and emerging potential Variants of Interest (pVOIs) together with their antigenic and evolutionary alterations. Using the establishment of Omicron and its current sublineages as an example, we demonstrate how CoVerage can be used to quickly identify and characterize such variants. CoVerage can facilitate the timely identification and assessment of future SARS-CoV-2 Variants of Concern.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.07.583829v1" target="_blank">In silico genomic surveillance by CoVerage predicts and characterizes SARS-CoV-2 Variants of Interest</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Rapid Degradation of the Human ACE2 Receptor Upon Binding and Internalization of SARS-Cov-2-Spike-RBD Protein</strong> -
|
|||
|
|
<div>
|
|||
|
|
It is widely accepted that the SARS-CoV-2 betacoronavirus infects humans through binding the human Angiotensin Receptor 2 (ACE2) that lines the nasal cavity and lungs, followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) cofactor. ACE2 binding is mediated by an approximately 200-residue portion of the SARS-CoV-2 extracellular spike protein, the receptor binding domain (RBD). Robust interactions are shown using a novel cell-based assay between an RBD membrane tethered-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein. Several observations were not predicted including, quick and sustained interactions leading to internalization of RBD fusion protein into the ACE2 cells and rapid downregulation of the ACE2-Cherry fluorescence. Targeted mutation in the RBD disulfide Loop 4 led to a loss of internalization for several variants tested. However, a secreted RBD did not cause ACE2 downregulation of ACE2-Cherry fluorescence. Thus, the membrane associated form of RBD found on the viral coat may have long-term system wide consequences on ACE2 expressing cells.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.07.583884v1" target="_blank">Rapid Degradation of the Human ACE2 Receptor Upon Binding and Internalization of SARS-Cov-2-Spike-RBD Protein</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Coronavirus Spike-RBD Variants Differentially Bind to the Human ACE2 Receptor</strong> -
|
|||
|
|
<div>
|
|||
|
|
The SARS-CoV-2 betacoronavirus infects people through binding the human Angiotensin Receptor 2 (ACE2), followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) and Furin cofactors. Analysis of the SARS-CoV-2 extracellular spike protein has suggested critical amino acids necessary for binding within a 197-residue portion, the receptor binding domain (RBD). A cell-based assay between a membrane tethered RBD-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein allowed for mutational intersection of both RBD and ACE2 proteins. Data shows Omicron BA.1 and BA.2 variants have altered dependency on the amino terminus of ACE2 protein and suggests multiple epitopes on both proteins stabilize their interactions at the Nt and internal region of ACE2. In contrast, the H-CoV-NL63 RBD is only dependent on the ACE2 internal region for binding. A peptide inhibitor approach to this internal region thus far have failed to block binding of RBDs to ACE2, suggesting that several binding regions on ACE2 are sufficient to allow functional interactions. In sum, the RBD binding surface of ACE2 appears relatively fluid and amenable to bind a range of novel variants.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.07.583944v1" target="_blank">Coronavirus Spike-RBD Variants Differentially Bind to the Human ACE2 Receptor</a>
|
|||
|
|
</div></li>
|
|||
|
|
<li><strong>Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1</strong> -
|
|||
|
|
<div>
|
|||
|
|
The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.
|
|||
|
|
</div>
|
|||
|
|
<div class="article-link article-html-link">
|
|||
|
|
🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.03.07.583823v1" target="_blank">Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1</a>
|
|||
|
|
</div></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Home-Based Circuit Training in Overweight/Obese Older Adult Patients With Knee Osteoarthritis and Type 2 Diabetes</strong> - <b>Conditions</b>: Aerobic Exercise; Strength Training; Glycemic Control; Blood Pressure; Oxidative Stress; Metabolic Syndrome <br/><b>Interventions</b>: Behavioral: 12-week home-based circuit training (HBCT); Behavioral: Standard of care (CONT) <br/><b>Sponsors</b>: Princess Nourah Bint Abdulrahman University <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC Platform Protocol</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG + Coordinated Care; Drug: IVIG Placebo + Coordinated Care; Drug: Ivabradine + Coordinated Care; Drug: Ivabradine Placebo + Coordinated Care; Drug: IVIG + Usual Care; Drug: IVIG Placebo + Usual Care; Drug: Ivabradine + Usual Care; Drug: Ivabradine Placebo + Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SVF for Treating Pulmonary Fibrosis Post COVID-19</strong> - <b>Conditions</b>: Pulmonary Fibrosis <br/><b>Interventions</b>: Biological: Autologous adipose-derived SVF IV administration <br/><b>Sponsors</b>: Michael H Carstens; Ministerio de Salud de Nicaragua; Wake Forest University; National Autonomous University of Nicaragua <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix B (Ivabradine)</strong> - <b>Conditions</b>: Long COVID; Long Covid19; Long Covid-19 <br/><b>Interventions</b>: Drug: Ivabradine; Drug: Ivabradine Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Enrolling by invitation</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)</strong> - <b>Conditions</b>: Long COVID; Long Coronavirus Disease 2019 (Covid19); Long Covid-19 <br/><b>Interventions</b>: Drug: IVIG (intravenous immunoglobulin); Drug: IVIG Placebo; Behavioral: Coordinated Care; Behavioral: Usual Care <br/><b>Sponsors</b>: Kanecia Obie Zimmerman <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Understanding Adaptive Immune Response After COVID-19 Vaccination Boosters to Improve Vaccination Strategies in Vulnerable Groups.</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Other: Analisys of cellular response and humoral response to SARS-CoV-2 vaccine booster doses <br/><b>Sponsors</b>: IRCCS Sacro Cuore Don Calabria di Negrar <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>COVIDVaxStories: Randomized Trial to Reduce COVID-19 Vaccine Hesitancy in Populations of Color</strong> - <b>Conditions</b>: Vaccine Hesitancy <br/><b>Interventions</b>: Behavioral: Storytelling; Behavioral: Learn More (Active Comparator) <br/><b>Sponsors</b>: University of Massachusetts, Worcester; Merck Sharp & Dohme LLC <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>An E-health Psychoeducation for People With Bipolar Disorders</strong> - <b>Conditions</b>: Bipolar Disorder; Psychoeducation; COVID-19 Pandemic <br/><b>Interventions</b>: Other: e-health psychoeducation <br/><b>Sponsors</b>: University of Cagliari; Alessandra Perra <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Sulfureous Water Therapy in Viral Respiratory Diseases</strong> - <b>Conditions</b>: Long-COVID; Post COVID-19 Condition; Chronic COVID-19 Syndrome; Post Acute Sequelae of COVID-19 <br/><b>Interventions</b>: Other: Inhalation of Sulfurous Thermal Water; Other: Inhalation of Sterile Distilled non-pyrogenic Water <br/><b>Sponsors</b>: University of Roma La Sapienza; Università degli studi di Roma Foro Italico; Queen Mary University of London; Bios Prevention Srl <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phase 3 Study to Evaluate the Safety and Immunogenicity of COVID-19 Vaccine and Influenza Combination Vaccine</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: CIC Vaccine Co-formulated tNIV2 , SARSCoV-2 rS and Matrix-M Adjuvant; Biological: Novavax COVID-19 Vaccine; Biological: Comparator Influenza Vaccine - Fluarix; Biological: Comparator Influenza Vaccine -Fluarix High Dose; Biological: Placebo 0.9% sodium chloride for injection <br/><b>Sponsors</b>: Novavax <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Evaluation of KGR Prescriptions in Suppressing COVID-19 Infection.</strong> - <b>Conditions</b>: Coronavirus Disease 2019; Severe Acute Respiratory Syndrome Coronavirus 2 Infection <br/><b>Interventions</b>: Combination Product: Kang Guan Recipe (Treat); Combination Product: Kang Guan Recipe (Placebo) <br/><b>Sponsors</b>: Sheng-Teng Huang <br/><b>Completed</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SHEN211 Tablets for the Treatment of Mild and Moderate Novel Corona Virus Infections (COVID-19)</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Drug: SHEN211 Tablets; Procedure: Placebo for SHEN211 Tablets <br/><b>Sponsors</b>: JKT Biopharma Co., Ltd. <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>INAVAC Vaccine Phase III (Immunobridging Study) in Healthy Population Aged 12 to 17 Years Old</strong> - <b>Conditions</b>: COVID-19 Pandemic; COVID-19 Vaccines <br/><b>Interventions</b>: Biological: INAVAC (Vaksin Merah Putih - UA-SARS CoV-2 (Vero Cell Inactivated) 5 µg <br/><b>Sponsors</b>: Dr. Soetomo General Hospital; Indonesia-MoH; Universitas Airlangga; PT Biotis Pharmaceuticals, Indonesia <br/><b>Recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study to Evaluate the Safety & Immunogenicity of IMNN-101 Administered in Healthy Adults Previously Vaccinated Against SARS-CoV-2</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: IMNN-101 <br/><b>Sponsors</b>: Imunon <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Immunogenicity and Safety Study of Self-amplifying mRNA COVID-19 Vaccine Administered With Influenza Vaccines in Adults</strong> - <b>Conditions</b>: COVID-19 <br/><b>Interventions</b>: Biological: ARCT-2303; Biological: Influenza vaccine; Biological: Influenza vaccine, adjuvanted; Other: Placebo <br/><b>Sponsors</b>: Arcturus Therapeutics, Inc.; Seqirus; Novotech (Australia) Pty Limited <br/><b>Not yet recruiting</b></p></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
|
|||
|
|
<ul>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Repurposing of Plant-based Antiviral Molecules for the Treatment of COVID-19</strong> - COVID-19, stemming from SARS-CoV-2, poses a formidable threat to global healthcare, with a staggering 77 million confirmed cases and 690,067 deaths recorded till December 24, 2023. Given the absence of specific drugs for this viral infection, the exploration of novel antiviral compounds becomes imperative. High-throughput technologies are actively engaged in drug discovery, and there is a parallel effort to repurpose plant-based molecules with established antiviral properties. In this context,…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Protective effect and mechanism of Qingfei Paidu decoction on myocardial damage mediated by influenza viruses</strong> - Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Decoding HiPSC-CM’s Response to SARS-CoV-2: mapping the molecular landscape of cardiac injury</strong> - CONCLUSION: SARS-CoV-2 infection in hiPSC-CMs is fundamentally mediated via mitochondrial dysfunction. Therapeutic interventions targeting mitochondrial dysfunction may alleviate the cardiovascular complications associated with SARS-CoV-2 infection.</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Identification of Phytochemicals from Arabian Peninsula Medicinal Plants as Strong Binders to SARS-CoV-2 Proteases (3CL(Pro) and PL(Pro)) by Molecular Docking and Dynamic Simulation Studies</strong> - We provide promising computational (in silico) data on phytochemicals (compounds 1-10) from Arabian Peninsula medicinal plants as strong binders, targeting 3-chymotrypsin-like protease (3CL^(Pro)) and papain-like proteases (PL^(Pro)) of SARS-CoV-2. Compounds 1-10 followed the Lipinski rules of five (RO5) and ADMET analysis, exhibiting drug-like characters. Non-covalent (reversible) docking of compounds 1-10 demonstrated their binding with the catalytic dyad (CYS145 and HIS41) of 3CL^(Pro) and…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II</strong> - Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhalation of ACE2-expressing lung exosomes provides prophylactic protection against SARS-CoV-2</strong> - Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity highlights the urgency of developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction becomes a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Neutrophil proteases are protective against SARS-CoV-2 by degrading the spike protein and dampening virus-mediated inflammation</strong> - Studies on severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have highlighted the crucial role of host proteases for viral replication and the immune response. The serine proteases furin and TMPRSS2 and lysosomal cysteine proteases were shown to facilitate virus entry by limited proteolytic processing of the spike (S) protein. While neutrophils are recruited to the lungs during COVID-19 pneumonia, little is known about the role of the neutrophil serine proteases (NSPs) cathepsin…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells</strong> - The transmembrane serine protease 2 (TMPRSS2) activates the outer structural proteins of a number of respiratory viruses including influenza A virus (IAV), parainfluenza viruses, and various coronaviruses for membrane fusion. Previous studies showed that TMPRSS2 interacts with the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), a cell surface protein that serves as an entry receptor for some coronaviruses. Here, by using protease activity assays, we determine that ACE2 increases the…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor</strong> - Protein-protein interactions (PPIs) offer great opportunities to expand the druggable proteome and therapeutically tackle various diseases, but remain challenging targets for drug discovery. Here, we provide a comprehensive pipeline that combines experimental and computational tools to identify and validate PPI targets and perform early-stage drug discovery. We have developed a machine learning approach that prioritizes interactions by analyzing quantitative data from binary PPI assays or…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure</strong> - The nucleocapsid (N) protein of SARS-CoV-2 is known to participate in various host cellular processes, including interferon inhibition, RNA interference, apoptosis, and regulation of virus life cycles. Additionally, it has potential as a diagnostic antigen and/or immunogen. Our research focuses on examining structural changes caused by mutations in the N protein. We have modeled the complete tertiary structure of native and mutated forms of the N protein using Alphafold2. Notably, the N protein…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Host-Directed Virus-Mimicking Particles Interacting with the ACE2 Receptor Competitively Block Coronavirus SARS-CoV-2 Entry</strong> - Herein, we fabricate host-directed virus-mimicking particles (VMPs) to block the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells through competitive inhibition enabled by their interactions with the angiotensin-converting enzyme 2 (ACE2) receptor. A microfluidic platform is developed to fabricate a lipid core of the VMPs with a narrow size distribution and a low level of batch-to-batch variation. The resultant solid lipid nanoparticles are decorated with an…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In Silico and In Vitro Screening of Some Pregnane Glycosides Isolated from Certain Caralluma Species as SARS-COV-2 Main Protease Inhibitors</strong> - SARS-CoV-2 caused pandemic represented a major risk for the worldwide human health, animal health and economy, forcing extraordinary efforts to discover drugs for its prevention and cure. Considering the extensive interest in the pregnane glycosides because of their diverse structures and excellent biological activities, we investigated them as antiviral agents against SARS-COV-2. We selected 21 pregnane glycosides previously isolated from the genus Caralluma from Asclepiadaceae family to be…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Angiotensin I and II Stimulate Cell Invasion of SARS-CoV-2: Potential Mechanism via Inhibition of ACE2 Arm of RAS</strong> - Angiotensin-converting enzyme 2 (ACE2), one of the key enzymes of the renin-angiotensin system (RAS), plays an important role in SARS-CoV-2 infection by functioning as a virus receptor. Angiotensin peptides Ang I and Ang II, the substrates of ACE2, can modulate the binding of SARS-CoV-2 Spike protein to the ACE2 receptor. In the present work, we found that co incubation of HEK-ACE2 and Vero E6 cells with the SARS-CoV-2 Spike pseudovirus (PVP) resulted in stimulation of the virus entry at low and…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Ginseng and ginsenosides on cardiovascular and pulmonary diseases; Pharmacological potentials for the coronavirus (COVID-19)</strong> - Since its outbreak in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has profoundly caused global morbidity and deaths. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has major complications in cardiovascular and pulmonary system. The increased rate of mortality is due to delayed detection of certain biomarkers that are crucial in the development of disease. Furthermore, certain proteins and enzymes in cellular signaling pathways play an…</p></li>
|
|||
|
|
<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome</strong> - The COVID-19 pandemic persists despite the availability of vaccines, and it is therefore crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of the oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and…</p></li>
|
|||
|
|
</ul>
|
|||
|
|
<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
|
|||
|
|
|
|||
|
|
|
|||
|
|
<script>AOS.init();</script></body></html>
|