CSF3 Is a Potential Drug Target for the Treatment of COVID-19.

Chao Fang,Wei Zhang,Jie Mei,Qianjin Liao,Yu-Ligh Liou,Huixiang Tian,Nayiyuan Wu,Dingchao Rong

doi:10.3389/fphys.2020.605792

Abstract

Coronavirus Disease 2019 (COVID-19) is an acute respiratory infectious disease that appeared at the end of 2019. As of July 2020, the cumulative number of infections and deaths have exceeded 15 million and 630,000, respectively. And new cases are increasing. There are still many difficulties surrounding research on the mechanism and development of therapeutic vaccines. It is urgent to explore the pathogenic mechanism of viruses to help prevent and treat COVID-19. In our study, we downloaded two datasets related to COVID-19 (GSE150819 and GSE147507). By analyzing the high-throughput expression matrix of uninfected human bronchial organoids and infected human bronchial organoids in the GSE150819, 456 differentially expressed genes (DEGs) were identified, which were mainly enriched in the cytokine–cytokine receptor interaction pathway and so on. We also constructed the protein–protein interaction (PPI) network of DEGs to identify the hub genes. Then we analyzed GSE147507, which contained lung adenocarcinoma cell lines (A549 and Calu3) and the primary bronchial epithelial cell line (NHBE), obtaining 799, 460, and 46 DEGs, respectively. The results showed that in human bronchial organoids, A549, Calu3, and NHBE samples infected with SARS-CoV-2, only one upregulated gene CSF3 was identified. Interestingly, CSF3 is one of the hub genes we previously screened in GSE150819, suggesting that CSF3 may be a potential drug target. Further, we screened potential drugs targeting CSF3 by MOE; the top 50 drugs were screened by flexible docking and rigid docking, with 37 intersections. Two antiviral drugs (Elbasvir and Ritonavir) were included; Elbasvir and Ritonavir formed van der Waals (VDW) interactions with surrounding residues to bind with CSF3, and Elbasvir and Ritonavir significantly inhibited CSF3 protein expression.

Highlights

Coronavirus Disease 2019, first detected in Wuhan, China, in December 2019, has been raging around the world from its detection through to current times (Kannan et al, 2020; Thompson, 2020)
To identify the significant pathways associated with the differentially expressed genes (DEGs) between uninfected human bronchial organoids and infected human bronchial organoids in GSE150819, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis by DAVID
The result showed that in GO enrichment analysis (Table 2), genes were enriched in biological processes (BP) of inflammatory response, immune response, and cell chemotaxis

Summary

Introduction

Coronavirus Disease 2019, first detected in Wuhan, China, in December 2019, has been raging around the world from its detection through to current times (Kannan et al, 2020; Thompson, 2020). On January 9, 2020, the World Health Organization (WHO) announced the discovery of the new coronavirus. This coronavirus was originally called 2019-nCoV and officially named SARS-CoV-2, which had never been found among humans. On February 11, 2020, the respiratory disease originating from SARS-CoV-2 infection was called COVID19 (Lu et al, 2020; Mahase, 2020). The virus was first discovered in Wuhan, there is still controversy about its specific origin (Andersen et al, 2020; Forster et al, 2020).

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