Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Abiraterone Acetate Attenuates SARS-CoV-2 Replication by Interfering with the Structural Nucleocapsid Protein

  • Kim, Jinsoo (Department of Microbiology, College of Medicine, Hallym University) ;
  • Hwang, Seok Young (College of Pharmacy, Natural Products Research Institute, Seoul National University) ;
  • Kim, Dongbum (Institute of Medical Science, College of Medicine, Hallym University) ;
  • Kim, Minyoung (Department of Microbiology, College of Medicine, Hallym University) ;
  • Baek, Kyeongbin (Department of Microbiology, College of Medicine, Hallym University) ;
  • Kang, Mijeong (Department of Microbiology, College of Medicine, Hallym University) ;
  • An, Seungchan (College of Pharmacy, Natural Products Research Institute, Seoul National University) ;
  • Gong, Junpyo (College of Pharmacy, Natural Products Research Institute, Seoul National University) ;
  • Park, Sangkyu (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Kandeel, Mahmoud (Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University) ;
  • Lee, Younghee (Department of Biochemistry, College of Natural Sciences, Chungbuk National University) ;
  • Noh, Minsoo (College of Pharmacy, Natural Products Research Institute, Seoul National University) ;
  • Kwon, Hyung-Joo (Department of Microbiology, College of Medicine, Hallym University)
  • Received : 2022.03.13
  • Accepted : 2022.04.14
  • Published : 2022.09.01
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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

Acknowledgement

We thank the National Culture Collection for Pathogens for providing the SARS-CoV-2 (hCoV-19/South Korea/KCDC03/2020, NCCP No. 43326). This research was supported by grants from the National Research Foundation (NRF-2020M3A9I2107294) funded by the Ministry of Science and ICT in the Republic of Korea. This work was also supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (Project No. GRANT672).

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