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KMID : 0606920220300050427
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Biomolecules & Therapeutics
2022 Volume.30 No. 5 p.427 ~ p.434
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Abiraterone Acetate Attenuates SARS-CoV-2 Replication by Interfering with the Structural Nucleocapsid Protein
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Kim Jin-Soo
Hwang Seok-Young
Kim Dong-Bum
Kim Min-Young
Baek Kyeong-Bin
Kang Mi-Jeong
An Seung-Chan
Gong Jun-Pyo
Park Sang-Kyu
Kandeel Mahmoud
Lee Young-Hee
Noh Min-Soo
Kwon Hyung-Joo
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Abstract
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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.
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KEYWORD
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Abiraterone acetate, Docking simulation, Drug repurposing, Nucleocapsid protein, SARS-CoV-2, Virtual screening
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