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MeSH Disease

HGNC Genes

SARS-CoV-2 proteins

ProteinE (144)

ProteinS (39)

ProteinN (33)

ComplexRdRp (17)

ProteinM (17)


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SARS-CoV-2 Proteins
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    Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation MESHD

    Authors: Gautam Anand; Alexandra M Perry; Celeste L Cummings; Emma St. Raymond; Regina A Clemens; Ashley L Steed

    doi:10.1101/2020.12.14.422710 Date: 2020-12-14 Source: bioRxiv

    SARS-CoV-2, the virus that has caused the COVID-19 pandemic MESHD, robustly activates the host immune system in critically ill MESHD patients. Understanding how the virus engages the immune system will facilitate the development of needed therapeutic strategies. Here we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins Spike (S PROTEIN) and Envelope (E) activate the key immune signaling interferon (IFN) pathway in both immune and epithelial cells independent of viral infection MESHD and replication. These proteins induce reactive oxidative species generation and increases in human and murine specific IFN-responsive cytokines and chemokines, similar to their upregulation in critically ill COVID-19 MESHD patients. Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators as the activation induced by S is dependent on IRF3 HGNC, TBK1 HGNC, and MYD88 HGNC while that of E is largely MYD88 HGNC independent. Furthermore, these viral surface proteins, specifically E, induced peribronchial inflammation MESHD and pulmonary vasculitis MESHD in a mouse model. Finally we show that the organized inflammatory infiltrates are dependent on type I IFN signaling, specifically in lung epithelial cells. These findings underscore the role of SARS-CoV-2 surface proteins, particularly the understudied E protein PROTEIN, in driving cell specific inflammation MESHD and their potential for therapeutic intervention. Author SummarySARS-CoV-2 robustly activates widespread inflammation MESHD, but we do not understand mechanistically how the virus engages the immune system. This knowledge will facilitate the development of critically needed therapeutic strategies to promote beneficial immune responses will dampening harmful inflammation MESHD. Here we demonstrate that SARS-CoV-2 surface proteins spike PROTEIN and envelope alone activated innate cell function and the interferon signaling pathway. This activation occurred in both immune and epithelial cells, and mechanistic studies demonstrated dependence on known key inflammatory signaling mediators, IRF3 HGNC, TBK1 HGNC, and MYD88 HGNC. In animal studies, we showed that these viral surface proteins induce epithelial cell IFN-dependent lung pathology, reminiscent to acute COVID-19 MESHD pulmonary infection MESHD. These findings underscore the need for further investigation into the role of SARS-CoV-2 surface proteins, particularly the understudied E protein PROTEIN, in driving cell specific inflammation MESHD.

    IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2

    Authors: Elizabeth C. Stahl; Connor A. Tsuchida; Jennifer R. Hamilton; Enrique Lin-Shiao; Shana L. McDevitt; Erica A. Moehle; Lea B. Witkowsky; C. Kimberly Tsui; Kathleen Pestal; Holly K. Gildea; Matthew McElroy; Amanda Keller; Iman Sylvain; Clara Williams; Ariana Hirsh; Alison Ciling; Alexander J. Ehrenberg; - SARS-CoV-2 consortium; Fyodor D. Urnov; Bradley R. Ringeisen; Petros Giannikopoulos; Jennifer A. Doudna

    doi:10.1101/2020.12.10.20247338 Date: 2020-12-11 Source: medRxiv

    Commonly used RT-qPCR-based SARS-CoV-2 diagnostics require 2-3 separate reactions or rely on detection of a single viral target, adding time and cost or risk of false-negative results. Currently, no test combines detection of widely used SARS-CoV-2 E- and N-gene PROTEIN targets and a sample control in a single, multiplexed reaction. We developed the IGI-LuNER RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene PROTEIN, E gene PROTEIN, and human RNase P (NER). This combined, cost-effective test can be performed in 384-well plates with detection sensitivity suitable for clinical reporting, and will aid in future sample pooling efforts, thus improving throughput of SARS-CoV-2 detection. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/20247338v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@74929corg.highwire.dtl.DTLVardef@1457971org.highwire.dtl.DTLVardef@2825ddorg.highwire.dtl.DTLVardef@1cde2b6_HPS_FORMAT_FIGEXP M_FIG C_FIG

    Binding of SARS-CoV-2 spike PROTEIN protein to ACE2 HGNC is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection MESHD studies.

    Authors: Kritika Khanna; Wilfred Raymond; Annabelle R Charbit; Jing Jin; Irina Gitlin; Monica Tang; Hannah S Sperber; Sergej Franz; Satish Pillai; Graham Simmons; John V Fahy; Suparerk Borwornpinyo; Arunee Thitithanyanont; Suradej Hongeng; Casey Barton Behravesh; Rebecca Fischer; Gabriel L Hamer; Marion Frankenberger; Lorenz Nowak; Katharina Heinig; Ina Koch; Mircea G Stoleriu; Anne Hilgendorff; Juergen Behr; Andreas Pichlmair; Benjamin Schubert; Fabian J Theis; Dirk H Busch; Herbert B Schiller; Kilian Schober; Evangelos J Giamarellos-Bourboulis; Timothy E Sweeney

    doi:10.1101/2020.12.08.415505 Date: 2020-12-08 Source: bioRxiv

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), and the SARS-CoV-2 spike PROTEIN protein is an envelope PROTEIN glycoprotein that binds angiotensin converting enzyme 2 as an entry receptor. The capacity of enveloped viruses to infect host MESHD cells depends on a precise thiol/disulfide balance in their surface glycoprotein complexes. To determine if cystines MESHD in the SARS-CoV-2 spike PROTEIN protein maintain a native binding interface that can be disrupted by drugs that cleave cystines, we tested if thiol-based drugs have efficacy in receptor binding and cell infection assays. We found that thiol-based drugs, cysteamine and WR-1065 (the active metabolite of amifostine) in particular, decrease binding of SARS-CoV-2 spike PROTEIN protein to its receptor, decrease the entry efficiency of SARS-CoV-2 spike PROTEIN pseudotyped virus, and inhibit SARS-CoV-2 live virus infection MESHD. Our findings uncover a vulnerability of SARS-CoV-2 to thiol-based drugs and provide rationale to test thiol-based drugs, especially cysteamine and amifostine, as novel treatments for COVID-19 MESHD. One Sentence SummaryThiol-based drugs decrease binding of SARS-CoV-2 spike PROTEIN protein to its receptor and inhibit SARS-CoV-2 cell entry.

    Galectin antagonist use in mild cases of SARS-CoV-2 cases; pilot feasibility randomised, open label, controlled trial

    Authors: ALBEN SIGAMANI; ALBEN SIGAMANI; MADHAVI KADAMBI; MATHU RUTHRA; SUDHISHMA SHIVAPRASAD; ANUP CHUGANI; HANA CHEN-WALDEN; THOMASKUTTY ALUMPARAMBILL; DAVID PLATT

    doi:10.1101/2020.12.03.20238840 Date: 2020-12-04 Source: medRxiv

    ImportanceNovel SARS-CoV-2 virus has infected nearly half a billion people across the world and is highly contagious. There is a need for a novel mechanism to block viral entry and stop its replication. BackgroundSpike protein N PROTEIN terminal domain (NTD) of the novel SARS-CoV-2 is essential for viral entry and replication in human cell. Thus the S1 NTD of human coronavirus family, which is similar to a galectin binding site - human galactose binding lectins, is a potential novel target for early treatment in COVID-19 MESHD. ObjectivesTo study the feasibility of performing a definitive trial of using galectin antagonist - Prolectin HGNC-M as treatment for mild, symptomatic, rRT-PCR positive, COVID-19 MESHD. Main outcomes and measuresCycle threshold (Ct) value is number of cycles needed to express fluorescence, on real time reverse transcriptase polymerase chain reaction. Ct values expressed for RNA polymerase (Rd/RP) gene +Nucleocapsid gene and the small envelope ( E) genes PROTEIN determine infectivity of the individual. A digital droplet PCR based estimation of the Nucleocapid genes (N1+N2) in absolute copies/L determines active viral replication. Design and interventionPilot Feasibility Randomised Controlled Open-Label, parallel arm, study. Oral tablets of Prolectin HGNC-M were administered along with the best practice, Standard of Care (SoC) and compared against SoC. Voluntarily, consenting individuals, age >18 years, and able to provide frequent nasopharyngeal and oropharyngeal swabs were randomly allocated by REDCap software. The intervention, Prolectin HGNC-M was administered as a multi dose regime of 4 gram tablets. Each tablet contained 2 grams of (1-6)-Alpha-D-mannopyranosil mixed with 2 grams of dietary fibre. Each participant took a single chewable tablet every hour, to a maximum of 10 hours in a day. Tablets were administered only during the daytime, for total of 5 days. ResultsThis pilot trial demonstrated the feasibility to recruit and randomize participants. By day 7, following treatment with Prolectin HGNC-M, Ct value of Rd/Rp + N gene PROTEIN increased by16.41 points, 95% (CI - 0.3527 to 32.48, p=0.047). Similarly, small envelope ( E) gene PROTEIN also increased by 17.75 points (95% CI;-0.1321 to 35.63, p = 0.05). The expression of N1, N2 genes went below detectable thresholds by day 3 (Mann Whitney U = 0.000, p<0.029). rRT-PCR testing done in the clinic on day 1, 7, and 14 had 3 participants (60%) turn negative by day 7 and all turned negative by day 14 and stayed negative until day 28. In the SoC group 2 participants had zero detectable viral loads at baseline, 2 participants tested negative on day 14, and the last participant tested remained positive on day 28. There were no serious adverse events, and all participants were clinically asymptomatic before day 28 with reactive immunoglobulin G (IgG). Trial relevanceThis pilot study proves that it is feasible and safe to perform a trial using a Galectin antagonist in COVID-19 MESHD. This is a novel mechanism for blocking viral entry and its subsequent replication. Trial RegistrationClinical Trials.gov identifier NCT04512027; CTRI ref. CTRI/2020/09/027833

    Amantadin has potential for the treatment of COVID-19 MESHD because it targets known and novel ion channels encoded by SARS-CoV-2

    Authors: Mads Gravers Jeppesen; Trine Lisberg Toft-Bertelsen; Thomas Nitschke Kledal; Mette Marie Rosenkilde

    doi:10.21203/rs.3.rs-121743/v1 Date: 2020-12-04 Source: ResearchSquare

    The dire need for therapies against SARS-CoV-2 infections MESHD is obvious and inspires strategies of repurposing drugs approved for other indications. Current examples are remdesivir (originally developed for ebola treatment) and steroids (anti-inflammatory treatment). Here we propose to use amantadine (an anti-influenza A drug) as a novel, cheap, readily available and effective way to treat COVID-19 MESHD because of its ability to inhibit known ( Protein E PROTEIN) and novel (Orf10) ion channels identified in the virus genome.

    T cell and antibody functional correlates of severe COVID-19 MESHD

    Authors: Krystle K.Q. Yu; Stephanie Fischinger; Malisa T. Smith; Caroline Atyeo; Deniz Cizmeci; Caitlin R. Wolf; Erik D. Layton; Jennifer K. Logue; Melissa S. Aguilar; Kiel Shuey; Carolin Loos; Jingyou Yu; Nicholas Franko; Robert Y. Choi; Anna Wald; Dan H. Barouch; David M. Koelle; Douglas Lauffenburger; Helen Y. Chu; Galit Alter; Chetan Seshadri

    doi:10.1101/2020.11.25.20235150 Date: 2020-11-30 Source: medRxiv

    Comorbid medical illnesses, such as obesity MESHD and diabetes MESHD, are associated with more severe COVID-19 MESHD, hospitalization, and death MESHD. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multi-parameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins PROTEIN in a convalescent cohort of COVID-19 MESHD subjects who were either hospitalized (n=20) or not hospitalized (n=40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4 T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4 T-cells and antibodies targeting the S1 domain of spike among subjects that were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2 which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19 MESHD. Our data suggest that isolated measurements of the magnitudes of spike-specific immune responses are likely insufficient to anticipate vaccine efficacy in high-risk populations.

    Rapid environmental monitoring, capture, and destruction activities of SARS-CoV-2 during the Covid-19 MESHD health emergency

    Authors: Roberto Marchetti; Martina Stella; Debjyoti Talukdar; Rosaria Erika Pileci

    doi:10.1101/2020.11.24.20237040 Date: 2020-11-27 Source: medRxiv

    SARS-CoV-2 pandemic is a health emergency for occupational healthcare workers at COVID19 MESHD hospital wards in Italy. The objective of the study was to investigate if U-Earth AIRcel bioreactors were effective in monitoring and improving air quality via detection, capture, and destruction of the SARS-CoV-2 virus, reducing the risk of transmission among healthcare workers. U-Earth AIRcel bioreactors are a demonstrated effective biomonitoring system. We implemented a methodological approach wherein they were placed at various hospitals treating COVID-19 MESHD patients in Italy. The detection of the SARS-CoV-2 virus was achieved through rapid biomonitoring testing of the solutes from the AIRcel bioreactors via SARS-CoV-2 rapid test antigen and consecutive reverse transcription-polymerase chain reaction (RT-PCR) analysis with the multiplex platform (XABT) and the Real-Time PCR Rotor-Gene. The marked presence of the SARS-CoV-2 virus was found in multiple water samples via the detection of ORF1ab PROTEIN + N and/or E gene PROTEIN involved in gene expression and cellular signaling of the SARS-CoV virus MESHD. The AIRcel bioreactors were able to neutralize the virus effectively as traces of the viruses were no longer found in multiple solute samples after an overnight period. Transmission of COVID-19 MESHD via bio-aerosols, transmitted by infected MESHD patients, remains a viable threat for health workers. AIRcel bioreactors allow for rapid biomonitoring testing for early virus detection within the environment, reducing the risk of exponential contagion exposure and maintaining good air quality without endangering health workers. This same protocol can also be extended to public spaces as a bio-monitoring tool for hotpots early detection.

    Identification of key genes and pathways in the hPSC-derived lungs infected by the SARS-CoV-2

    Authors: Hanming Gu; Gongsheng Yuan

    doi:10.21203/rs.3.rs-114578/v1 Date: 2020-11-23 Source: ResearchSquare

    Coronavirus disease 2019 MESHD ( COVID-19 MESHD) is caused by the severe acute respiratory syndrome coronavirus 2 MESHD (SARS-CoV-2), which has led to numerous infections MESHD and deaths MESHD in the world. Our research is to explore the differentially expressed genes (DEGs) and signaling pathways in hPSC-derived lungs by using a bioinformatics method to clarify their potential pathogenesis. The gene expression profile of GSE155241 dataset was originally created by using an Illumina NovaSeq 6000 (Homo sapiens) platform. Functional categories and significant pathways were identified by the KEGG and GO analysis. The results suggested that brain disorders MESHD and mitochondrial dysfunctions MESHD are the main signaling pathways affected by the SARS-CoV-2 infection MESHD. Furthermore, key genes e PROTEIN.g. CDC20 HGNC, NCBP1 HGNC and inhibitors e.g. MEK1 HGNC-2-inhibitor, tivozanib may paly critical roles in COVID-19 MESHD. Therefore, our study provides insights into the treatment of COVID-19 MESHD and related disorders.

    Clinical evaluation of the Roche/SD Biosensor rapid antigen test with symptomatic, non-hospitalized patients in a municipal health service drive-through testing site.

    Authors: Zsofia Igloi; Jans Velzing; Janko van Beek; David van de Vijver; Georgina Aron; Roel Ensing; Kimberley Benschop; Wanda Han; Timo Boelsums; Marion Koopmans; Corine Geurtsvankessel; Richard Molenkamp

    doi:10.1101/2020.11.18.20234104 Date: 2020-11-20 Source: medRxiv

    BackgroundRapid detection of infectious individuals is essential in stopping the further spread of SARS-CoV-2. Although rapid antigen test is not as sensitive as the gold standard RT-PCR, the time to result is decreased by day(s), strengthening the effectiveness of contact tracing. MethodsThe Roche/SD Biosensor lateral flow antigen rapid test was evaluated in a mild symptomatic population at a large drive through testing site. A second nasopharyngeal swab was directly tested with the rapid test on site and results were compared to RT-PCR and virus culture. Date of onset and symptoms were analysed using data from a clinical questionnaire. ResultsWe included 970 persons with complete data. Overall sensitivity and specificity were 84.9% (CI95% 79.1-89.4) and 99.5% (CI95% 98.7-99.8) which translated into a positive predictive value of 97.5% (CI95% 94.0-99.5) under the current regional PCR positivity of 19.2%. Sensitivity for people with high loads of viral RNA (ct <30, 2.17E+05 E gene PROTEIN copy/ml) and who presented within 7 days since symptom onset increased to 95.8% (CI95% 90.5-98.2). Band intensity and time to result correlated strongly with viral load thus strong positive bands could be read before the recommended time. Around 98% of all viable specimen with ct <30 were detected successfully indicating that the large majority of infectious people can be captured with this test. ConclusionAntigen rapid tests can detect mildly symptomatic cases in the early phase of disease thereby identifying the most infectious individuals. Using this assay can have a significant value in the speed and effectiveness of SARS-CoV-2 outbreak management. SummaryO_LIPeople with early onset and high viral load were detected with 98.2% sensitivity. C_LIO_LI97% of individuals in which virus could be cultured were detected by the rapid test. C_LIO_LIThis test is suitable to detect mild symptomatic cases. C_LI

    SARS-CoV-2 in a Tropical Area of Colombia, a Remarkable Conversion of Presymptomatic to Symptomatic People Impacts Public Health

    Authors: Caty Martinez; Hector Serrano; Salim Mattar; Álvaro A. Faccini-Martínez; Veronica Contreras; Ketty Galeano; Yesica Botero; Yonairo Herrera; Alejandra Garcia; Evelin Garay; Ricardo Rivero; Hector Contreras; Yesica Lopez; Camilo Guzman; Jorge Miranda; German Arrieta

    doi:10.21203/rs.3.rs-111785/v1 Date: 2020-11-19 Source: ResearchSquare

    The ability of SARS-CoV-2 to remain in asymptomatic individuals facilitates its dissemination and makes its control difficult. Objective. To establish a cohort of asymptomatic individuals, change to the symptomatic state, and determine the most frequent clinical manifestations. Methods. Between April 9 and August 9, 2020, molecular diagnosis of SARS-CoV-2 infection MESHD was confirmed in 154 asymptomatic people in contact with subjects diagnosed with COVID-19 MESHD. Nasopharyngeal swabs were performed on these people in different hospitals in Córdoba, the Caribbean area of Colombia. The genes E PROTEIN, RdRp PROTEIN, and N were amplified with RT-qPCR. Based on the molecular results and the Cq values, the patients were subsequently followed up through telephone calls to verify their health conditions. Results. Overall, of 154 asymptomatic individuals, 103 (66.9%) remained asymptomatic, and 51 (33.1%) changed to symptomatic. The most frequent clinical manifestations in young people were anosmia MESHD and arthralgia MESHD; in adults, they were cough, ageusia, and odynophagia; in the elderly were epigastralgia, dyspnea MESHD, and headache MESHD. Mortality was 8%. Conclusions. A proportion of 33% of presymptomatic individuals was found, of which four of them died. This high rate could indicate a silent transmission, contributing significantly to the increase in the epidemic associated with SARS-CoV-2.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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