Corpus overview


MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinS (13)


SARS-CoV-2 Proteins
    displaying 1 - 10 records in total 17
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    Insertions in SARS-CoV-2 genome caused by template switch and duplications give rise to new variants of potential concern

    Authors: Sofiya K Garushyants; Igor B Rogozin; Eugene V. Koonin

    doi:10.1101/2021.04.23.441209 Date: 2021-04-26 Source: bioRxiv

    The appearance of multiple new SARS-CoV-2 variants during the winter of 2020-2021 is a matter of grave concern. Some of these new variants, such as B.1.351 and B.1.1.17, manifest higher infectivity and virulence than the earlier SARS-CoV-2 variants, with potential dramatic effects on the course of the COVID-19 pandemic MESHD. So far, analysis of new SARS-CoV-2 variants focused primarily on point nucleotide substitutions and short deletions that are readily identifiable by comparison to consensus genome sequences. In contrast, insertions have largely escaped the attention of researchers although the furin HGNC site insert in the spike protein PROTEIN is thought to be a determinant of SARS-CoV-2 virulence MESHD and other inserts might have contributed to coronavirus pathogenicity as well. Here, we investigate insertions in SARS-CoV-2 genomes and identify 141 unique inserts of different lengths. We present evidence that these inserts reflect actual virus variance rather than sequencing errors. Two principal mechanisms appear to account for the inserts in the SARS-CoV-2 genomes, polymerase slippage and template switch that might be associated with the synthesis of subgenomic RNAs. We show that inserts in the Spike glycoprotein PROTEIN can affect its antigenic properties and thus have to be monitored. At least, two inserts in the N-terminal domain of the Spike (ins246DSWG and ins15ATLRI) that were first detected in January 2021 are predicted to lead to escape from neutralizing antibodies whereas other inserts might result in escape from T-cell immunity.

    SARS-CoV-2 Viremia MESHD is Associated with Distinct Proteomic Pathways and Predicts COVID-19 MESHD Outcomes

    Authors: Yijia Li; Alexis M Schneider; Arnav Mehta; Moshe Sade-Feldman; Kyle R Kays; Matteo Gentili; Nicole C Charland; Anna LK Gonye; Irena Gushterova; Hargun K Khanna; Thomas J LaSalle; Kendall M Lavin-Parsons; Brendan M Lilley; Carl L Lodenstein; Kasidet Manakongtreecheep; Justin D Margolin; Brenna N McKaig; Blair A Parry; Maricarmen Rojas-Lopez; Brian C Russo; Nihaarika Sharma; Jessica Tantivit; Molly F Thomas; James Regan; James P Flynn; Alexandra-Chloe Villani; Nir Hacohen; Marcia B Goldberg; Michael R Filbin; Jonathan Z Li

    doi:10.1101/2021.02.24.21252357 Date: 2021-02-26 Source: medRxiv

    Background: Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2) plasma viremia MESHD has been associated with severe disease and death in coronavirus disease MESHD coronavirus disease 2019 MESHD ( COVID-19 MESHD) in small-scale cohort studies. The mechanisms behind this association remain elusive. Methods: We evaluated the relationship between SARS-CoV-2 viremia MESHD, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 MESHD emergency department participants. SARS-CoV-2 viral load was measured using qRT-PCR based platform. Proteomic data were generated with Proximity Extension Assay (PEA) using the Olink platform. Results: Three hundred participants with nucleic acid test-confirmed COVID-19 MESHD were included in this study. Levels of plasma SARS-CoV-2 viremia MESHD at the time of presentation predicted adverse disease outcomes, with an adjusted odds ratio (aOR) of 10.6 (95% confidence interval [CI] 4.4, 25.5, P<0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and aOR of 3.9 (95%CI 1.5, 10.1, P=0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia MESHD, including upregulation of SARS-CoV-2 entry factors ( ACE2 HGNC, CTSL HGNC, FURIN HGNC), heightened markers of tissue damage to the lungs, gastrointestinal tract, endothelium/vasculature and alterations in coagulation pathways. Conclusions: These results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia MESHD that underlies its ability to predict COVID-19 MESHD disease outcomes.

    Multiple Sites on SARS-CoV-2 Spike PROTEIN SARS-CoV-2 Spike MESHD Protein are Susceptible to Proteolysis by Cathepsins B, K, L, S, and V

    Authors: Keval Bollavaram; Tiffanie Leeman; Akhil Kulkarni; Sophia Upshaw; Maggie Lee; Jiabei Yang; Hannah Song; Manu O Platt

    doi:10.1101/2021.02.17.431617 Date: 2021-02-17 Source: bioRxiv

    SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic MESHD. Proteases are central to the infection process of SARS-CoV-2 MESHD. Cleavage of the spike protein PROTEIN on the virus capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2 HGNC, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein PROTEIN must be identified. We identified amino acid sequences in all regions of spike protein PROTEIN, including the S1/S2 region critical for activation and viral entry, that are susceptible to cleavage by furin HGNC and cathepsins B, K, L, S, and V using PACMANS, a computational platform that identifies and ranks preferred sites of proteolytic cleavage on substrates, and verified with molecular docking analysis and immunoblotting to determine if binding of these proteases can occur on the spike protein PROTEIN that were identified as possible cleavage sites. Together, this study highlights cathepsins B, K, L, S, and V for consideration in SARS-CoV-2 infection MESHD and presents methodologies by which other proteases can be screened to determine a role in viral entry. This highlights additional proteases to be considered in COVID-19 MESHD studies, particularly regarding exacerbated damage in inflammatory preconditions where these proteases are generally upregulated.

    D614G Substitution of SARS-CoV-2 Spike MESHD SARS-CoV-2 Spike PROTEIN Protein Increases Syncytium Formation and Viral Transmission via Enhanced Furin HGNC-mediated Spike Cleavage

    Authors: Ya-Wen Cheng; Tai-Ling Chao; Chiao-Ling Li; Sheng-Han Wang; Han-Chieh Kao; Ya-Min Tsai; Hurng-Yi Wang; Chi-Ling Hsieh; Pei-Jer Chen; Sui-Yuan Chang; Shiou-Hwei Yeh

    doi:10.1101/2021.01.27.428541 Date: 2021-01-28 Source: bioRxiv

    Since the D614G substitution in the spike (S) of SARS-CoV-2 emerged, the variant strain underwent rapid expansion to become the most abundant strain worldwide. Therefore, this substitution may provide an advantage of viral spreading. To explore the mechanism, we analyzed 18 viral isolates containing S proteins PROTEIN with either G614 or D614. Both the virus titer and syncytial phenotype were significantly increased in S-G614 than in S-D614 isolates. We further showed increased cleavage of S at the furin HGNC substrate site, a key event that promotes syncytium, in S-G614 isolates. These functions of the D614G substitution were validated in cells expressing S protein PROTEIN. The effect on syncytium was abolished by furin HGNC inhibitor treatment and mutation of the furin HGNC-cleavage site, suggesting its dependence on cleavage by furin HGNC. Our study provides a mechanistic explanation for the increased transmissibility of S-G614 containing SARS-CoV-2 through enhanced furin HGNC-mediated S cleavage, which increases membrane fusion and virus infectivity.

    Fibrinolysis influences SARS-CoV-2 infection MESHD in ciliated cells

    Authors: Myoung Ryoul Park; Chunmei Cai; Min-Jung Seo; Hong-Tae Yun; Soo-Kwon Park; Man-Soo Choi; Chang-Hwan Park; Jung Kyung Moon

    doi:10.1101/2021.01.07.425801 Date: 2021-01-08 Source: bioRxiv

    Rapid spread of COVID-19 MESHD has caused an unprecedented pandemic worldwide, and an inserted furin HGNC site in SARS-CoV-2 spike PROTEIN protein (S PROTEIN) may account for increased transmissibility. Plasmin HGNC, and other host proteases, may cleave the furin HGNC site of SARS-CoV-2 S protein PROTEIN and {gamma} subunits of epithelial sodium channels ({gamma} ENaC), resulting in an increment in virus infectivity and channel activity. As for the importance of ENaC in the regulation of airway surface and alveolar fluid homeostasis MESHD, whether SARS-CoV-2 will share and strengthen the cleavage network with ENaC proteins at the single-cell level is urgently worthy of consideration. To address this issue, we analyzed single-cell RNA sequence (scRNA-seq) datasets, and found the PLAU HGNC (encoding urokinase plasminogen activator), SCNN1G HGNC ({gamma}ENaC), and ACE2 HGNC (SARS-CoV-2 receptor) were co-expressed in alveolar epithelial MESHD, basal, club, and ciliated epithelial cells. The relative expression level of PLAU HGNC, TMPRSS2 HGNC, and ACE2 HGNC were significantly upregulated in severe COVID-19 MESHD patients and SARS-CoV-2 infected MESHD cell lines using Seurat and DESeq2 R packages. Moreover, the increments in PLAU HGNC, FURIN HGNC, TMPRSS2 HGNC, and ACE2 HGNC were predominately observed in different epithelial cells and leukocytes. Accordingly, SARS-CoV-2 may share and strengthen the ENaC fibrinolytic proteases network in ACE2 HGNC positive airway and alveolar MESHD epithelial cells, which may expedite virus infusion into the susceptible cells and bring about ENaC associated edematous respiratory condition MESHD.

    The polybasic cleavage site in the SARS-CoV-2 spike PROTEIN modulates viral sensitivity to Type I IFN and IFITM2


    doi:10.1101/2020.12.19.423592 Date: 2020-12-20 Source: bioRxiv

    The cellular entry of severe acute respiratory syndrome MESHD-associated coronaviruses types 1 and 2 (SARS-CoV-1 and -2) requires sequential protease processing of the viral spike glycoprotein PROTEIN (S). The presence of a polybasic cleavage site in SARS-CoV-2 S at the S1/S2 boundary has been suggested to be a factor in the increased transmissibility of SARS-CoV-2 compared to SARS-CoV-1 by facilitating maturation of the S precursor by furin HGNC-like proteases in the producer cells rather than endosomal cathepsins in the target. We investigate the relevance of the polybasic cleavage site in the route of entry of SARS-CoV-2 and the consequences this has for sensitivity to interferons, and more specifically, the IFN-induced transmembrane (IFITM) protein family that inhibit entry of diverse enveloped viruses. We found that SARS-CoV-2 is restricted predominantly by IFITM2 HGNC and the degree of this restriction is governed by route of viral entry. Removal of the cleavage site in the spike protein PROTEIN renders SARS-CoV-2 entry highly pH- and cathepsin-dependent in late endosomes where, like SARS-CoV-1 S MESHD, it is more sensitive to IFITM2 HGNC restriction. Furthermore, we find that potent inhibition of SARS-CoV-2 replication by type I but not type II IFNs is alleviated by targeted depletion of IFITM2 HGNC expression. We propose that the polybasic cleavage site allows SARS-CoV-2 to mediate viral entry in a pH-independent manner, in part to mitigate against IFITM-mediated restriction and promote replication and transmission. This suggests therapeutic strategies that target furin HGNC-mediated cleavage of SARS-CoV-2 S MESHD may reduce viral replication through the activity of type I IFNs. IMPORTANCEThe furin HGNC cleavage site in the S protein PROTEIN is a distinguishing feature of SARS-CoV-2 and has been proposed to be a determinant for the higher transmissibility between individuals compared to SARS-CoV-1. One explanation for this is that it permits more efficient activation of fusion at or near the cell surface rather than requiring processing in the endosome of the target cell. Here we show that SARS-CoV-2 is inhibited by antiviral membrane protein IFITM2 HGNC, and that the sensitivity is exacerbated by deletion of the furin HGNC cleavage site which restricts viral entry to low pH compartments. Furthermore, we find that IFITM2 HGNC is a significant effector of the antiviral activity of type I interferons against SARS-CoV-2 replication. We suggest one role of the furin HGNC cleavage site is to reduce SARS-CoV-2 sensitivity to innate immune restriction, and thus may represent a potential therapeutic target for COVID-19 MESHD treatment development.

    A Meta-analysis of Comorbidities in COVID-19 MESHD: Which Diseases increase the Susceptibility of SARS-CoV-2 Infection MESHD?

    Authors: Srinivasan Ramachandran; Manoj Kumar Singh; Ahmed Mobeen; Amit Chandra; Sweta Joshi

    id:10.20944/preprints202009.0486.v1 Date: 2020-09-21 Source:

    Background: Comorbidities have been frequently reported in COVID-19 MESHD patients, which often lead to more severe outcomes. The underlying molecular mechanisms behind these clinical observations have not yet been explained. Herein, we investigated the disease-specific gene expression signatures that may induce susceptibility to SARS-CoV-2 infection MESHD. Methods: We studied 30 frequently occurring acute, chronic, or infectious diseases of recent times that have shown comorbidity in one or another respiratory disease MESHD(s) caused by pathogenic human infecting coronaviruses, especially SARS-CoV-2. We retrieved array-based gene expression data for each disease and control from relevant datasets. Subsequently, all the datasets were quantile normalized, and log-2 transformed data was used for analysis. Results The expression of ACE2 HGNC receptor and host proteases, namely FURIN HGNC and TMPRSS2 HGNC that are essential for cellular entry of SARS-CoV-2, was upregulated in all six studied subtypes of leukemia MESHD (hereafter, referred as leukemia MESHD). The expression of ACE2 HGNC was also increased in psoriasis MESHD, lung cancer MESHD, Non-alcoholic fatty liver disease MESHD ( NAFLD MESHD), breast cancer MESHD, and pulmonary arterial hypertension MESHD patients. The expression of FURIN HGNC was higher in psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, and in type II diabetic liver MESHD, whereas it was lowered in breast cancer MESHD. Similarly, the expression of TMPRSS2 HGNC was increased during lung cancer MESHD and type II diabetes MESHD; it was decreased during psoriasis MESHD, NAFLD MESHD, lung cancer MESHD, breast cancer MESHD, and cervical cancer MESHD.Furthermore, a heightened expression of genes that are involved in immune response was observed in leukemia MESHD patients, as shown by the higher expression of IFNA2 HGNC, IFNA8 HGNC, IFNA10 HGNC, IFNA14 HGNC, IFNA16 HGNC, IFNA21 HGNC, IFNB1 HGNC, CXCL10 HGNC, and IL6 HGNC. The expression of JAK1 HGNC, STAT1 HGNC, IL6 HGNC, and CXCL10 HGNC was higher in NAFLD MESHD. Besides, JAK1 HGNC and STAT1 HGNC were upregulated in type II diabetic muscles MESHD. In addition, most of the upregulated genes in COVID-19 MESHD patients showed a similar trend in leukemia MESHD, NAFLD MESHD, and psoriasis MESHD. Furthermore, SARS-CoV-2, SARS-CoV MESHD and MERS CoV, were found to commonly alter two genes, namely, CARBONIC ANHYDRASE 11 and CLUSTERIN.Conclusions: The genes that may confer susceptibility to SARS-CoV-2 infection MESHD are mostly upregulated in leukemia MESHD patients; hence, leukemia MESHD patients are relatively more susceptible to develop COVID-19 MESHD, followed by other chronic disorders MESHD, such as, NAFLD MESHD, type II diabetes MESHD, psoriasis MESHD, and hypertension MESHD. This study identifies key genes that are altered in the studied diseases types, which may aid in the infection of SARS-CoV-2 MESHD and underlie COVID-19 MESHD associated comorbidities.

    Human airway organoids model SARS-CoV-2 high infectiousness and evasion of interferon response

    Authors: Jie Zhou; Man Chun Chiu; Cun LI; Xiaojuan Liu; Xiaoyu Zhao; Dong Wang; Yuxuan Wei; Hin Chu; Jian-Piao Cai; Cyril Chik-Yan Yip; Vincent Poon; Ivy Chan; Kenneth Kak-Yuen Wong; Jasper Fuk-Woo Chan; Zhiwei Chen; Honglin Chen; Hans Clevers; Kwok-Yung Yuen

    doi:10.21203/ Date: 2020-08-28 Source: ResearchSquare

    SARS-CoV-2 is more infectious and transmissible in humans than SARS-CoV, despite the genetic relatedness and sharing the same cellular receptor. We sought to assess whether human airway organoids can model SARS-CoV-2 infection MESHD in the human airway and elucidate the cellular basis underlying its higher transmissibility. We demonstrate that SARS-CoV-2 can establish a productive infection in human airway organoids, in which ciliated cell and basal cell are infected. Wildtype SARS-CoV-2 carrying a furin HGNC cleavage motif exhibits comparable replication kinetics to a mutant virus without the motif. Human airway organoids sustain higher replication of SARS-CoV-2 than SARS-CoV MESHD, whereas interferon response is more potently induced in the latter than the former. Overall, human airway organoids can model SARS-CoV-2 infection MESHD and recapitulate the disposable role of furin HGNC cleavage motif for virus transmission in humans. SARS-CoV-2 stealth growth and evasion of interferon response may underlie pre-symptomatic virus shedding in COVID-19 MESHD patients, leading to its high infectiousness and transmissibility.

    Furin HGNC cleavage of SARS-CoV-2 Spike PROTEIN promotes but is not essential for infection and cell-cell fusion

    Authors: Guido Papa; Donna Mallery; Anna Albecka; Lawrence Welch; Jerome Cattin-Ortola; Jakub Luptak; David Paul; Harvey McMahon; Ian G. Goodfellow; Andrew P Carter; Sean P Munro; Leo C James

    doi:10.1101/2020.08.13.243303 Date: 2020-08-14 Source: bioRxiv

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects MESHD cells by binding to the host cell receptor Ace2 HGNC and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2 HGNC, which processes the viral Spike (S) protein PROTEIN to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin HGNC in order to prime S protein PROTEIN for TMPRSS2 HGNC processing. Here we show that CRISPR-Cas9 knockout of furin HGNC reduces, but does not prevent, the production of infectious SARS-CoV-2 MESHD virus. Comparing S processing in furin HGNC knockout cells to multibasic site mutants reveals that while loss of furin HGNC substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S MESHD S protein PROTEIN also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin HGNC in either donor or acceptor cells reduces, but does not prevent, TMPRSS2 HGNC-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin HGNC promotes both SARS-CoV-2 infectivity MESHD and cell-cell spread it is not essential, suggesting furin HGNC inhibitors will not prevent viral spread.

    Elovanoid-N32 or RvD6-isomer decrease ACE2 HGNC and binding of S protein PROTEIN RBD after injury or INFγ in the eye

    Authors: Thang L. Pham; Jiucheng He; Azucena H. Kakazu; Jorgelina Calandria; Khanh V. Do; Robert Nshimiyimana; Nicos A. Petasis; Haydee E.P. Bazan; Nicolas G. Bazan

    doi:10.21203/ Date: 2020-08-07 Source: ResearchSquare

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD that causes coronavirus disease 2019 MESHD ( COVID-19 MESHD) has resulted in a pandemic affecting the most vulnerable in society, triggering a public health crisis and economic tall around the world. Effective treatments to mitigate this virus infection are needed. Since the eye is a route of virus entrance, we use an in vivo rat model of corneal inflammation MESHD as well as human corneal epithelial cells in culture challenged with IFNγ HGNC to study this issue. We explore ways to block the receptor-binding domain (RBD) of SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN ( S) protein PROTEIN to angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC). Elovanoid (ELV)-N32 or Resolvin D6-isomer (RvD6i), among the lipid mediators studied, consistently decreased the expression of the ACE2 HGNC receptor, furin HGNC, and integrins in damaged corneas or IFNγ HGNC stimulated human corneal epithelial cells (HCEC). There was also a concomitant decrease in the binding of spike RBD with the lipid treatments. Concurrently, we uncovered that the lipid mediators also attenuated the expression of cytokines that participate in the cytokine storm, hyper-inflammation MESHD and senescence programming. Thus, the bioactivity of these lipid mediators will contribute to opening therapeutic avenues for COVID-19 MESHD by counteracting virus attachment and entrance to the eye and other cells and the ensuing disruptions of homeostasis. 

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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