Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2022.037
Abiraterone Acetate Attenuates SARS-CoV-2 Replication by Interfering with the Structural Nucleocapsid Protein
Jinsoo Kim1,†, Seok Young Hwang2,†, Dongbum Kim3,†, Minyoung Kim1, Kyeongbin Baek1, Mijeong Kang1, Seungchan An2, Junpyo Gong2, Sangkyu Park4, Mahmoud Kandeel5,6, Younghee Lee4, Minsoo Noh2,* and Hyung-Joo Kwon1,3,*
1Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252,
2College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826,
3Institute of Medical Science, College of Medicine, Hallym University, Chuncheon 24252,
4Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea
5Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-hofuf 31982, Saudi Arabia
6Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University, Kafrelshikh 33516, Egypt
*E-mail: hjookwon@hallym.ac.kr (Kwon HJ), minsoonoh@snu.ac.kr (Noh M)
Tel: +82-33-248-2635 (Kwon HJ), +82-02-880-2481 (Noh M)
Fax: +82-33-241-3640 (Kwon HJ), +82-02-880-2482 (Noh M)
The first three authors contributed equally to this work.
Received: March 13, 2022; Revised: April 1, 2022; Accepted: April 14, 2022; Published online: May 13, 2022.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.
Keywords: Abiraterone acetate, Docking simulation, Drug repurposing, Nucleocapsid protein, SARS-CoV-2, Virtual screening


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