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

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

doi:10.3389/fphys.2020.605792

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

Front Physiol. 2021 Jan 22:11:605792. doi: 10.3389/fphys.2020.605792. eCollection 2020.

Authors

Chao Fang^{1

2}, Jie Mei¹, Huixiang Tian³, Yu-Ligh Liou¹, Dingchao Rong⁴, Wei Zhang¹, Qianjin Liao², Nayiyuan Wu^{1

2}

Affiliations

¹ Hunan Key Laboratory of Pharmacogenetics, Department of Clinical Pharmacology, Xiangya Hospital, Institute of Clinical Pharmacology, Central South University, Changsha, China.
² Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
³ Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, China.

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.

Keywords: COVID-19; CSF3; MOE; elbasvir; ritonavir.