tetano
Editor, Senior Moderator
Mol Cells
. 2021 Sep 14.
doi: 10.14348/molcells.2021.076. Online ahead of print.
Asunaprevir, a Potent Hepatitis C Virus Protease Inhibitor, Blocks SARS-CoV-2 Propagation
Yun-Sook Lim[SUP] 1 [/SUP], Lap P Nguyen[SUP] 1 2 [/SUP], Gun-Hee Lee[SUP] 3 [/SUP], Sung-Geun Lee[SUP] 3 [/SUP], Kwang-Soo Lyoo[SUP] 3 [/SUP], Bumseok Kim[SUP] 4 [/SUP], Soon B Hwang[SUP] 1 2 [/SUP]
Affiliations
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: COVID-19; SARS-CoV-2; asunaprevir; drug repurposing; hepatitis C virus.
. 2021 Sep 14.
doi: 10.14348/molcells.2021.076. Online ahead of print.
Asunaprevir, a Potent Hepatitis C Virus Protease Inhibitor, Blocks SARS-CoV-2 Propagation
Yun-Sook Lim[SUP] 1 [/SUP], Lap P Nguyen[SUP] 1 2 [/SUP], Gun-Hee Lee[SUP] 3 [/SUP], Sung-Geun Lee[SUP] 3 [/SUP], Kwang-Soo Lyoo[SUP] 3 [/SUP], Bumseok Kim[SUP] 4 [/SUP], Soon B Hwang[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34518443
- DOI: 10.14348/molcells.2021.076
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: COVID-19; SARS-CoV-2; asunaprevir; drug repurposing; hepatitis C virus.