BackgroundCoronavirus Disease 2019 (COVID-19) respiratory disease 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 treatment. Moreover, TCM and CWM are important data source for developing new drug targets and promote strategies treat SARS-CoV-2 infections. However, many studies have analyzed the therapeutic mechanism of CWM or TCM alone for COVID-19, it is still unclear the interaction mechanism between TCM and CWM on COVID-19.MethodsThis paper integrates network pharmacology and GEO database to mine and identify COVID-19 molecular therapeutic targets, providing potential targets and new ideas for COVID-19 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: STAT1, IL1B, IL6, IL8, PTGS2 and NFKBIA, and these genes were significantly downregulated in A549 and NHBE cells by SARS-CoV-2 infection. Moreover, chemical interaction and molecular docking analysis of hub genes showed that folic acid might as be potential therapeutic drug for COVID-19 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 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 molecular therapy, on the other hand, it provides ideas for the analysis of interaction mechanism between virus and host.