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SARS-CoV-2 proteins

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    Network of “drug-target-SARS-CoV-2 Related Genes” Through Integrated Analysis of Pharmacology and Geo Database

    Authors: Jin ping Hou; Yong heng Wang; Yu meng Chen; Yi hao Chen; Xiao Zhu; Rui si Qin; Tingting Chen

    doi:10.21203/rs.3.rs-117894/v1 Date: 2020-11-28 Source: ResearchSquare

    BackgroundCoronavirus Disease MESHD Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) respiratory disease MESHD rapidly caused a global pandemic and social and economic disruption. The combination of Traditional Chinese medicine (TCM) and Conventional Western medicine (CWM) is more effective for COVID-19 MESHD treatment. Moreover, TCM and CWM are important data source for developing new drug targets and promote strategies treat SARS-CoV-2 infection MESHD SARS-CoV-2 infection MESHDs. However, many studies have analyzed the therapeutic mechanism of CWM or TCM alone for COVID-19 MESHD, it is still unclear the interaction mechanism between TCM and CWM on COVID-19 MESHD.MethodsThis paper integrates network pharmacology and GEO database to mine and identify COVID-19 MESHD molecular therapeutic targets, providing potential targets and new ideas for COVID-19 MESHD gene therapy and new drug development. It includes: 1) using TCMSP, TTD, PubChem and CTD databases to analyze drug interactions and associated phenotypes for SARS-CoV-2, to correlate drug and disease interaction mechanisms to screen key drug targets; 2) using GEO database to correlate differential genes and drug targets to screen potential antiviral gene therapy targets, to construct regulatory network and key points of SARS-CoV-2 therapeutic drugs; 3) using computer simulation of molecular docking to screen virus-related proteins for new drugs. ResultsIntegrated analysis of network pharmacology discovered that baicalein, estrone and quercetin are the pivotal active ingredients in TCM and CWM. Combining drug target genes in pharmacology database and virus induced genes in GEO database, the result showed the core hub genes related to COVID-19 MESHD: STAT1 HGNC, IL1B HGNC, IL6 HGNC, IL8 HGNC, PTGS2 HGNC and NFKBIA HGNC, and these genes were significantly downregulated in A549 and NHBE cells by SARS-CoV-2 infection MESHD. Moreover, chemical interaction and molecular docking analysis of hub genes showed that folic acid might as be potential therapeutic drug for COVID-19 MESHD treatment, and SARS-CoV-2 nucleocapsid phosphoprotein was a potential drug target. The network of “drug-target-SARS-CoV-2 related genes” provide noval potential compounds and targets for further studies of SARS-CoV-2.ConclusionsIntegrated analysis of network pharmacology and big data mining provided noval potential compounds and targets for further studies of SARS-CoV-2. Our research implied folic acid and SARS-CoV-2 N as therapeutic target in TCM and CWM. Our research also suggests that targeting SARS-CoV-2 N MESHD N protein PROTEIN is likely to be a common mechanism of TCM and CWM. On the one hand, the identification of pivotal genes provides a target for COVID-19 MESHD molecular therapy, on the other hand, it provides ideas for the analysis of interaction mechanism between virus and host.

    Role of IgG against N-protein PROTEIN of SARS-CoV2 in COVID19 MESHD clinical outcomes

    Authors: Mayank Batra; Runxia Tian; Chongxu Zhang; Emile Clarence; Camila Sofia Sacher; Justin Nestor Miranda; Justin Rafa O De La Fuente; Megan Mathew; Desmond Green; Sayari Patel; Maria Virginia Perez Bastidas; Sara Haddadi; Mukunthan Murthi; Miguel Santiago Gonzalez; Shweta Kambali; Kayo HM Santos; Huda Asif; Farzaneh Modarresi; Mohammad Faghihi; Mehdi Mirsaeidi

    doi:10.1101/2020.09.23.20197251 Date: 2020-09-24 Source: medRxiv

    The Nucleocapsid Protein (N PROTEIN Protein) of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein PROTEIN is detectable in the serum of infected MESHD patients. The effect of high titers of IgG against N-protein PROTEIN on clinical outcomes of SARS-CoV2 disease MESHD has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including MICU admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum IgG against the N protein PROTEIN and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6 HGNC, and presentation with dyspnea MESHD were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 HGNC levels were independently associated with in-hospital mortality. Anti- N protein PROTEIN IgG was detected in the serum of 55 (55%) patients at the time of admission. A high concentration of antibodies, defined as signal to cut off ratio (S/Co)> 1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio> 1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein PROTEIN of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection MESHD.

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MeSH Disease
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