Prediction of potential therapeutic drugs against SARS-CoV-2 by using Connectivity Map based on transcriptome data

W.-Y. Chen, Z.-X. Fang, X.-D. Lv, Q.-H. Zhou, M. Yao, M. Deng

Department of Respiration, the First Hospital of Jiaxing and Affiliated Hospital of Jiaxing University, Jiaxing, China. dengmigaa@163.com

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• Infectious Diseases

OBJECTIVE: Transcriptome data related to severe acute respiratory syndrome-related coronavirus 2 (a novel coronavirus discovered in 2019, SARS-CoV-2) in GEO database were downloaded. Based on the data, influence of SARS-CoV-2 on human cells was analyzed and potential therapeutic compounds against the SARS-CoV-2 were screened.

MATERIALS AND METHODS: R package “DESeq2” was used for differential gene analysis on the data of cells infected or non-infected with SARS-CoV-2. The “ClusterProfiler” package was used for GO functional annotation and KEGG pathway enrichment analysis of the differentially expressed genes (DEGs). A protein-protein interaction (PPI) network of the DEGs was constructed through STRING website, and the key subset in the PPI network was identified after visualization by Cytoscape software. Connectivity Map (CMap) database was used to screen known compounds that caused genomic change reverse to that caused by SARS-CoV-2.

RESULTS: By intersecting DEGs in two datasets, a total of 145 DEGs were screened out, among which 136 genes were upregulated and 9 genes were downregulated in SARS-CoV-2-infected cells. Functional enrichment analyses revealed that these genes were mainly associated with the pathways involved in viral infection, inflammatory response, and immunity. The CMap research found that there were three compounds with a median_tau_score less than -90, namely triptolide, tivozanib and daunorubicin.

CONCLUSIONS: SARS-CoV-2 can cause abnormal changes in a large number of molecules and related signaling pathways in human cells, among which IL-17 and TNF signaling pathways may play a key role in pathogenic process of SARS-CoV-2. Here, three compounds that may be effective for the treatment of SARS-CoV-2 were screened, which would provide new options for improving treatment of patients infected with SARS-CoV-2.

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