Abiraterone Acetate Attenuates SARS-CoV-2 Replication by Interfering with the Structural Nucleocapsid Protein

• Published in: Biomolecules & therapeutics Vol. 30; no. 5; pp. 427 - 434
• Main Authors: Kim, Jinsoo, Hwang, Seok Young, Kim, Dongbum, Kim, Minyoung, Baek, Kyeongbin, Kang, Mijeong, An, Seungchan, Gong, Junpyo, Park, Sangkyu, Kandeel, Mahmoud, Lee, Younghee, Noh, Minsoo, Kwon, Hyung-Joo
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society of Applied Pharmacology 01.09.2022; 한국응용약물학회
• Subjects: Original; 약학; Drug repurposing; Virtual screening; SARS-CoV-2; Docking simulation; Nucleocapsid protein; Abiraterone acetate
• ISSN: 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2022.037

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 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.