Abiraterone Acetate Attenuates SARS-CoV-2 Replication by Interfering with the Structural Nucleocapsid Protein
10.4062/biomolther.2022.037
- Author:
Jinsoo KIM
1
;
Seok Young HWANG
;
Dongbum KIM
;
Minyoung KIM
;
Kyeongbin BAEK
;
Mijeong KANG
;
Seungchan AN
;
Junpyo GONG
;
Sangkyu PARK
;
Mahmoud KANDEEL
;
Younghee LEE
;
Minsoo NOH
;
Hyung-Joo KWON
Author Information
1. Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2022;30(5):427-434
- CountryRepublic of Korea
- Language:English
-
Abstract:
The drug repurposing strategy has been applied to the development of emergency COVID-19 therapeutic medicines. Current drug repurposing approaches have been directed against RNA polymerases and viral proteases. Recently, we found that the inhibition of the interaction between the SARS-CoV-2 structural nucleocapsid (N) and spike (S) proteins decreased viral replication. In this study, drug repurposing candidates were screened by in silico molecular docking simulation with the SARS-CoV-2 structural N protein. In the ChEMBL database, 1994 FDA-approved drugs were selected for the in silico virtual screening against the N terminal domain (NTD) of the SARS-CoV-2 N protein. The tyrosine 109 residue in the NTD of the N protein was used as the center of the ligand binding grid for the docking simulation. In plaque forming assays performed with SARS-CoV-2 infected Vero E6 cells, atovaquone, abiraterone acetate, and digoxin exhibited a tendency to reduce the size of the viral plagues without affecting the plaque numbers. Abiraterone acetate significantly decreased the accumulation of viral particles in the cell culture supernatants in a concentration-dependent manner. In addition, abiraterone acetate significantly decreased the production of N protein and S protein in the SARS-CoV-2-infected Vero E6 cells. In conclusion, abiraterone acetate has therapeutic potential to inhibit the viral replication of SARS-CoV-2.
