Asunaprevir, a Potent Hepatitis C Virus Protease Inhibitor, Blocks SARS-CoV-2 Propagation
Yun-Sook Lim 1, Lap P. Nguyen 1,2, Gun-Hee Lee 3, Sung-Geun Lee 3, Kwang-Soo Lyoo 3, Bumseok Kim 4, and Soon B. Hwang 1,2,*
1Laboratory of RNA Viral Diseases, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea, 2Ilsong Institute of Life Science, Hallym University, Seoul 07247, Korea, 3Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea, 4College of Veterinary Medicine, Jeonbuk National University, Iksan 54531, Korea
Received March 29, 2021; Revised July 19, 2021; Accepted July 20, 2021.; Published online September 14, 2021.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become a global health concern. Various SARS-CoV-2 vaccines have been developed and are being used for vaccination worldwide. However, no therapeutic agents against coronavirus disease 2019 (COVID-19) have been developed so far; therefore, new therapeutic agents are urgently needed. In the present study, we evaluated several hepatitis C virus direct-acting antivirals as potential candidates for drug repurposing against COVID-19. Theses include asunaprevir (a protease inhibitor), daclatasvir (an NS5A inhibitor), and sofosbuvir (an RNA polymerase inhibitor). We found that asunaprevir, but not sofosbuvir and daclatasvir, markedly inhibited SARS-CoV-2-induced cytopathic effects in Vero E6 cells. Both RNA and protein levels of SARS-CoV-2 were significantly decreased by treatment with asunaprevir. Moreover, asunaprevir profoundly decreased virion release from SARS-CoV-2-infected cells. A pseudoparticle entry assay revealed that asunaprevir blocked SARS-CoV-2 infection at the binding step of the viral life cycle. Furthermore, asunaprevir inhibited SARS-CoV-2 propagation in human lung Calu-3 cells. Collectively, we found that asunaprevir displays broad-spectrum antiviral activity and therefore might be worth developing as a new drug repurposing candidate for COVID-19.
Keywords: asunaprevir, COVID-19, drug repurposing, hepatitis C virus, SARS-CoV-2


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31 August 2021 Volume 44,
Number 8, pp. 541~625
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