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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.

    Cyclooxgenase-2 is induced by SARS-CoV-2 infection MESHD but does not affect viral entry or replication

    Authors: Jennifer S. Chen; Mia Madel Alfajaro; Jin Wei; Ryan D. Chow; Renata B Filler; Stephanie C. Eisenbarth; Craig B Wilen; Li Hui Tan; Beihua Dong; Konstantinos Dionysios Alysandratose; Jesse Huang; James N Palmer; Nithin D Adappa; Michael A Kohanski; Darrell N Kotton; Robert H Silverman; Wenli Yang; Edward Morrisey; Noam Cohen; Susan R Weiss; David C. Jackson; Nathan W Bartlett; Francesca Mercuri; Miles W Carroll; Sonam T. Nyatsatsang; Alexander L. Greninger; Ansuman T. Satpathy; John S Pauk; Scott D. Boyd; James R. Heath

    doi:10.1101/2020.09.24.312769 Date: 2020-09-25 Source: bioRxiv

    Identifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection MESHD and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain MESHD and inflammation MESHD, could modulate both SARS-CoV-2 infection MESHD and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 HGNC ( COX-1 HGNC) and cyclooxygenase-2 HGNC ( COX-2 HGNC), which mediate the production of prostaglandins (PGs). PGE2, one of the most abundant PGs, has diverse biological roles in homeostasis and inflammatory responses. Previous studies have shown that NSAID treatment or inhibition of PGE2 receptor signaling leads to upregulation of angiotensin-converting enzyme 2 HGNC ( ACE2 HGNC), the cell entry receptor for SARS-CoV-2, thus raising concerns that NSAIDs could increase susceptibility to infection. COX/PGE2 signaling has also been shown to regulate the replication of many viruses, but it is not yet known whether it plays a role in SARS-CoV-2 replication. The purpose of this study was to dissect the effect of NSAIDs on COVID-19 MESHD in terms of SARS-CoV-2 entry MESHD and replication. We found that SARS-CoV-2 infection MESHD induced COX-2 HGNC upregulation in diverse human cell culture and mouse systems. However, suppression of COX-2/PGE2 signaling by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 HGNC expression, viral entry, or viral replication. Our findings suggest that COX-2 HGNC signaling driven by SARS-CoV-2 may instead play a role in regulating the lung inflammation MESHD and injury observed in COVID-19 MESHD patients.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins

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