Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (115)

ProteinN (28)

NSP5 (11)

ComplexRdRp (10)

ProteinE (7)


SARS-CoV-2 Proteins
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    Uncovering cryptic pockets in the SARS-CoV-2 spike PROTEIN glycoprotein

    Authors: Lorena Zuzic; Firdaus Samsudin; Aishwary Tukaram Shivgan; Palur V Raghuvamsi; Jan K Marzinek; Alister Boags; Conrado Pedebos; Nikhil Kumar Tulsian; Jim Warwicker; Paul MacAry; Max Crispin; Syma Khalid; Ganesh S Anand; Peter J Bond

    doi:10.1101/2021.05.05.442536 Date: 2021-05-05 Source: bioRxiv

    The recent global COVID-19 pandemic MESHD has prompted a rapid response in terms of vaccine and drug development targeting the viral pathogen, severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2). In this work, we modelled a complete membrane-embedded SARS-CoV-2 spike PROTEIN SARS-CoV-2 spike MESHD ( S) protein PROTEIN, the primary target of vaccine and therapeutics development, based on available structural data and known glycan content. We then used molecular dynamics ( MD MESHD) simulations to study the system in the presence of benzene probes designed to enhance discovery of cryptic, potentially druggable pockets on the S protein PROTEIN surface. We uncovered a novel cryptic pocket with promising druggable properties located underneath the 617-628 loop, which was shown to be involved in the formation of S protein PROTEIN multimers on the viral surface. A marked multi-conformational behaviour of this loop in simulations was validated using hydrogen-deuterium exchange mass spectrometry (HDX-MS) experiments, supportive of opening and closing dynamics. Interestingly, the pocket is also the site of the D614G mutation, known to be important for SARS-CoV-2 fitness MESHD, and within close proximity to mutations in the novel SARS-CoV-2 strains B.1.1.7 and B.1.1.28, both of which are associated with increased transmissibility and severity of infection. The pocket was present in systems emulating both immature and mature glycosylation states, suggesting its druggability may not be dependent upon the stage of virus maturation. Overall, the predominantly hydrophobic nature of the cryptic pocket, its well conserved surface, and proximity to regions of functional relevance in viral assembly and fitness MESHD are all promising indicators of its potential for therapeutic targeting. Our method also successfully recapitulated hydrophobic pockets in the receptor binding domain and N-terminal domain associated with detergent or lipid binding in prior cryo-electron microscopy (cryo-EM) studies. Collectively, this work highlights the utility of the benzene mapping approach in uncovering potential druggable sites on the surface of SARS-CoV-2 targets.

    Point of care testing for detection of coronaviruses including SARS-CoV-2 from saliva without treating RNA in advance MESHD

    Authors: Masaaki Muraoka; Osamu Kawaguchi; Mikio Mizukoshi; Shunsuke Sejima

    doi:10.1101/2021.05.01.21256441 Date: 2021-05-04 Source: medRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) outbreak was reported to the WHO (World Health Organization) as an outbreak on end of 2019, afterwards pandemic on the worldwide in 2020. Severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) has be reported it to cause COVID-19 MESHD, and highly transmissible. Therefore, it is important that it is rapidly and continuously detected and monitored on site so that the infection is prevented. Namely, POCT (point of care testing) may be important to control cross infection of SARS-CoV-2 MESHD. At present, the routine confirmation of SARS-CoV-2 is based on detection of sequence unique in the virus RNA by nucleic acid amplification tests (NAATs) such as rRT-PCR. Taking POCT into account, it is clear that it takes time and labour very much or much. Thus, it was our purpose this time to contribute to develop POCT for microbes such as SARS-CoV-2, and thus needed to improve NAATs method. First, combining the mobile real-time RT-PCR (rRT-PCR) device PCR1100 with the appropriate rRT-PCR reagent, we found that it is possible to detect RNA of SARS-CoV-2 for less 14 minutes with equivalent accuracy to conventional devices. Next, we found that the above method made it possible for us to detect coronaviruses by direct rRT-PCR without pre-treatments. Furthermore, it also made clear that coronaviruses in saliva could be detected by the similar direct rRT-PCR method. Hence, it was concluded that this method made it possible to detect virus in saliva without treating in advance (extraction, purification, concentration, etc.), and moreover, samples would be able to be collected with non-invasive. For this reason, we suggest that this method is useful for POCT of coronaviruses including SARS-CoV-2.


    Authors: Riccardo Polosa; V. Tomaselli; P. Ferrara; A. C. Romeo; S. Rust; D. Saitta; F. Caraci; C. Romano; M. Thangaraju; P. Zuccarello; J. Rose; M. Ferrante; J. Belsey; F. Cibella; E. Interlandi; R. Ferri

    doi:10.1101/2021.04.29.21256236 Date: 2021-05-03 Source: medRxiv

    After the global spread of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), research has highlighted several aspects of the pandemic, focusing on clinical features and risk factors associated with infection and disease severity. However, emerging results on the role of smoking in SARS-CoV-2 infection MESHD susceptibility or COVID-19 MESHD outcomes are conflicting, and their robustness remains uncertain. In this context, this project aims at quantifying the proportion of SARS-CoV-S MESHD antibody seroprevalence, studying the changes in antibody levels over time, and analyzing the association between smoking status and infection using seroprevalence data. The added value of this research is that the current smoking status of the population to be studied will be biochemically verified, in order to avoid the bias associated with self-reported smoking status. As such, the results from this survey may provide actionable metric to study the role of smoking in SARS-CoV-2 spread, and therefore implement the most appropriate public health measures to control the pandemic. The research design involves a 6-month prospective cohort study with serial sampling of the same individuals. Each participant will be surveyed about their demographics and COVID-19 MESHD-related information, and blood sampling will be collected upon recruitment and at specified follow-up time points (namely, after 8 and 24 weeks). Blood samples will be screened for the presence of SARS-CoV-2 specific antibodies and serum cotinine. Overall, we expect to find a higher prevalence of antibodies in individuals at high-risk for viral exposure (i.e., healthcare or other essential workers), according to previous literature, and to refine current estimates on the association between smoking status and SARS-CoV-2/ COVID-19 MESHD. Our results may serve as a reference for future clinical research and the methodology could be exploited in public health sectors and policies.

    Age-dependent association between SARS-CoV-2 cases reported by passive surveillance and viral load in wastewater

    Authors: Ryosuke Omori; Fuminari Miura; Masaaki Kitajima

    doi:10.1101/2021.04.30.21256366 Date: 2021-05-03 Source: medRxiv

    The true number of individuals infected with severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) is difficult to estimate using a case-reporting system (i.e., passive surveillance) alone because of asymptomatic infection. While wastewater-based epidemiology has been implemented as an alternative/additional monitoring tool to reduce reporting bias, the relationship between passive and wastewater surveillance data has yet to be explicitly examined. Since there is strong age dependency in the symptomatic ratio of SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs, this study aimed to estimate i) an age-dependent association between the number of reported cases and the viral load in wastewater and ii) the time lag between those time series. The viral load in wastewater was modeled as a combination of contributions from different age groups' virus shedding, incorporating the delay, and fitted with daily case count data collected from the Massachusetts Department of Public Health and SARS-CoV-2 RNA concentrations in wastewater collected by the Massachusetts Water Resources Authority. The estimated lag between the time series of viral loads in wastewater and of reported cases was 10.8 days (95% confidence interval =[10.2, 11.6]) for wastewater treatment plant's northern area and 8.8 days [8.4, 9.1] for southern area. The estimated contribution rate of a reported case to the viral load in wastewater in the 0-19 yr age group was 0.38 [0.35, 0.41] for northern area and 0.40 [0.37, 0.43] for southern area, that in the 80+ yr age group was 0.67 [0.65, 0.69] for northern area and 0.51 [0.49, 0.52] for southern area. The estimated lag between those time series suggested the predictability of reported cases ten days later using viral loads in wastewater. The contribution of a reported case in passive surveillance to the viral load in wastewater differed by age, suggesting a large variation in viral shedding kinetics among age groups.

    SARS-CoV-2 spike PROTEIN protein induces brain pericyte immunoreactivity in absence of productive viral infection

    Authors: Rayan Khaddaj-Mallat; Natija Aldib; Anne-Sophie Paquette; Aymeric Ferreira; Sarah Lecordier; Maxime Bernard; Armen Saghatelyan; Ayman ElAli

    doi:10.1101/2021.04.30.442194 Date: 2021-05-03 Source: bioRxiv

    COVID-19 MESHD is a respiratory disease MESHD caused by severe acute respiratory syndrome coronavirus-2 MESHD (SARS-CoV-2). COVID-19 MESHD pathogenesis causes vascular-mediated neurological disorders MESHD via still elusive mechanisms. SARS-CoV-2 infects host MESHD cells by binding to angiotensin-converting enzyme 2 HGNC (ACE2), a transmembrane receptor that recognizes the viral spike (S) protein PROTEIN. Brain pericytes were recently shown to express ACE2 at the neurovascular interface, outlining their possible implication in microvasculature injury MESHD in COVID-19 MESHD. Yet, pericyte responses to SARS-CoV-2 is still to be fully elucidated. Using cell-based assays, we report that ACE2 HGNC expression in human brain vascular pericytes is highly dynamic and is increased upon S protein PROTEIN stimulation. Pericytes exposed to S protein PROTEIN underwent profound phenotypic changes translated by increased expression of contractile and myofibrogenic proteins, namely -smooth muscle actin (- SMA HGNC), fibronectin HGNC, collagen I, and neurogenic locus notch homolog protein-3 HGNC ( NOTCH3 HGNC). These changes were associated to an altered intracellular calcium (Ca2+) dynamic. Furthermore, S protein PROTEIN induced lipid peroxidation, oxidative and nitrosative stress in pericytes as well as triggered an immune reaction translated by activation of nuclear factor-kappa-B ( NF-{kappa}B HGNC) signalling pathway, which was potentiated by hypoxia MESHD, a condition associated to vascular comorbidities, which exacerbate COVID-19 MESHD pathogenesis. S protein PROTEIN exposure combined to hypoxia MESHD enhanced the production of pro-inflammatory cytokines involved in immune cell activation and trafficking, namely interleukin-8 HGNC ( IL-8 HGNC), IL-18 HGNC, macrophage migration inhibitory factor HGNC ( MIF HGNC), and stromal cell-derived factor-1 HGNC ( SDF-1 HGNC). Finally, we found that S protein PROTEIN could reach the mouse brain via the intranasal route and that reactive ACE2-expressing pericytes are recruited to the damaged tissue undergoing fibrotic scarring in a mouse model of cerebral multifocal micro-occlusions, a main reported vascular-mediated neurological condition associated to COVID-19 MESHD. Our data demonstrate that the released S protein PROTEIN is sufficient to mediate pericyte immunoreactivity, which may contribute to microvasculature injury MESHD in absence of a productive viral infection MESHD. Our study provides a better understanding for the possible mechanisms underlying cerebrovascular disorders MESHD in COVID-19 MESHD, paving the way to develop new therapeutic interventions.

    Original antigenic sin responses to heterologous Betacoronavirus spike proteins PROTEIN are observed in mice following intramuscular administration, but are not apparent in children following SARS-CoV-2 infection MESHD

    Authors: Stacey A. Lapp; Venkata Viswanadh Edara; Austin Lu; Lilin Lai; Laila Hussaini; Ann Chahroudi; Larry J. Anderson; Mehul S. Suthar; Evan J. Anderson; Christina A. Rostad

    doi:10.1101/2021.04.29.21256344 Date: 2021-04-30 Source: medRxiv

    Background: The effects of pre-existing endemic human coronavirus (HCoV) immunity on SARS-CoV-2 serologic and clinical responses are incompletely understood. Objectives: We sought to determine the effects of prior exposure to HCoV Betacoronavirus HKU1 spike MESHD spike protein PROTEIN on serologic responses to SARS-CoV-2 spike PROTEIN protein after intramuscular administration in mice. We also sought to understand the baseline seroprevalence of HKU1 spike antibodies in healthy children and to measure their correlation with SARS-CoV-2 binding and neutralizing antibodies in children hospitalized with acute coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) or multisystem inflammatory syndrome MESHD ( MIS-C MESHD). Methods: Groups of 5 mice were injected intramuscularly with two doses of alum-adjuvanted HKU1 spike followed by SARS-CoV-2 spike PROTEIN; or the reciprocal regimen of SARS-Cov-2 spike followed by HKU1 spike. Sera collected 21 days following each injection was analyzed for IgG antibodies to HKU1 spike, SARS-CoV-2 PROTEIN SARS-CoV-2 spike MESHD spike, and SARS-CoV-2 PROTEIN neutralization. Sera from children hospitalized with acute COVID-19 MESHD, MIS-C or healthy controls (n=14 per group) were analyzed for these same antibodies. Results: Mice primed with SARS-CoV-2 spike PROTEIN SARS-CoV-2 spike MESHD and boosted with HKU1 spike developed high titers of SARS-CoV-2 binding and neutralizing antibodies; however, mice primed with HKU1 spike and boosted with SARS-CoV-2 spike PROTEIN were unable to mount neutralizing antibodies to SARS-CoV-2. HKU1 spike antibodies were detected in all children with acute COVID-19 MESHD, MIS-C, and healthy controls. Although children with MIS-C had significantly higher HKU1 spike titers than healthy children (GMT 37239 vs. 7551, P=0.012), these titers correlated positively with both SARS-CoV-2 binding (r=0.7577, P<0.001) and neutralizing (r=0.6201, P=0.001) antibodies. Conclusions: Prior murine exposure to HKU1 spike protein PROTEIN completely impeded the development of neutralizing antibodies to SARS-CoV-2, consistent with original antigenic sin. In contrast, the presence of HKU1 spike IgG antibodies in children with acute COVID-19 MESHD or MIS-C was not associated with diminished neutralizing antibody responses to SARS-CoV-2.

    Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein PROTEIN

    Authors: Jan-Philipp Mallm; Christian Bundschuh; Heeyoung Kim; Niklas Weidner; Simon Steiger; Isabelle Lander; Kathleen Börner; Katharina Bauer; Daniel Hübschmann; Vladimir Benes; Tobias Rausch; Nayara Trevisan Doimo de Azevedo; Anja Telzerow; Katharina Laurence Jost; Sylvia Parthé; Paul Schnitzler; Michael Boutros; Barbara Müller; Ralf Bartenschlager; Hans-Georg Kräusslich; Karsten Rippe

    doi:10.1101/2021.04.27.21254849 Date: 2021-04-29 Source: medRxiv

    Variants of severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2) are replacing the initial wild-type strain, jeopardizing current efforts to contain the pandemic. Amino acid exchanges in the spike protein PROTEIN are of particular concern as they can render the virus more transmissible or reduce vaccine efficacy. Here, we conducted whole genome sequencing of SARS-CoV MESHD 2 positive samples from the Rhine-Neckar district in Germany during January-March 2021. We detected a total of 166 samples positive for a variant with a distinct mutational pattern in the spike gene comprising L18F, L452R, N501Y, A653V, H655Y, D796Y and G1219V with a later gain of A222V. This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. These observations strongly argue for continuous and comprehensive monitoring of SARS CoV MESHD 2 evolution on a population level.

    Predicted structural mimicry of spike receptor-binding motifs from highly pathogenic human coronaviruses

    Authors: Christopher A Beaudoin; Arian Rokkum Jamasb; Ali Alsulami; Liviu Copoiu; Andries J van Tonder; Sharif Hala; Bridget P Bannerman; Sherine E Thomas; Sundeep Chaitanya Vedithi; Pedro H M Torres; Tom L Blundell

    doi:10.1101/2021.04.23.441187 Date: 2021-04-26 Source: bioRxiv

    Viruses often encode proteins that mimic host proteins in order to facilitate infection. Little work has been done to understand the potential mimicry of the SARS-CoV-2, SARS-CoV MESHD, and MERS-CoV spike proteins MESHD spike proteins PROTEIN, particularly the receptor-binding motifs, which could be important in determining tropism of the virus. Here, we use structural bioinformatics software to characterize potential mimicry of the three coronavirus spike protein PROTEIN receptor-binding motifs. We utilize sequence-independent alignment tools to compare structurally known or predicted three-dimensional protein models with the receptor-binding motifs and verify potential mimicry with protein docking simulations. Both human and non-human proteins were found to be similar to all three receptor-binding motifs. Similarity to human proteins may reveal which pathways the spike protein PROTEIN is co-opting, while analogous non-human proteins may indicate shared host interaction partners and overlapping antibody cross-reactivity. These findings can help guide experimental efforts to further understand potential interactions between human and coronavirus proteins.

    Rapid detection of SARS CoV-2 N501Y mutation in clinical samples

    Authors: Sirwan M.A. Al-Jaf; Sherko Subhan Niranji

    doi:10.1101/2021.04.17.21255656 Date: 2021-04-20 Source: medRxiv

    Severe acute respiratory syndrome coronavirus-2 MESHD (SARS CoV-2) variants poses major threats in increasing infectivity, transmission, mortality of Coronavirus Disease 2019 MESHD ( Covid-19 MESHD). Additionally, SARS CoV-2 variants resist antibody neutralizations or may abolish vaccine efficacies. Researches to develop economical and fast methods will support the developing or poor countries to challenge the Covid-19 pandemic MESHD via tracking common mutations that may help to deploy the vaccination programs and control the virus. Current study has developed a novel low-cost rapid technique, exploiting real time PCR probes and conventional PCR specific primers, to identify N501Y mutation, which was independently emerged in the UK, South African and Brazilian variants. Currently, these variants tend to spread to all over the world and seem to be more infectious, transmissible and fatal. This study helps tracking the N501Y mutation for understanding its clinical and epidemiological characteristics, in those countries where sequencing facilities are lacking or expensive. Further study should focus on other common mutations in the variants of concerns of SARS CoV-2 MESHD.

    Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection MESHD

    Authors: Martina Severa; Roberta Antonina Diotti; Marilena Paola Etna; Fabiana Rizzo; Stefano Fiore; Daniela Ricci; Marco Iannetta; Alessandro Sinigaglia; Alessandra Lodi; Nicasio Mancini; Elena Criscuolo; Massimo Clementi; Massimo Andreoni; Stefano Balducci; Luisa Barzon; Paola Stefanelli; Nicola Clementi; Eliana Coccia

    doi:10.1101/2021.04.17.440278 Date: 2021-04-19 Source: bioRxiv

    SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 MESHD ( COVID-19 MESHD) progression. Indeed, critically ill MESHD patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure MESHD. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7 HGNC/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19 MESHD. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2 HGNC-indipendent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 HGNC marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected MESHD subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 MESHD display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 MESHD patients.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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