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.
【저자키워드】 COVID-19, Drug repurposing, SARS-CoV-2, asunaprevir, hepatitis C virus., 【초록키워드】 Treatment, coronavirus disease, Drug repurposing, Coronavirus disease 2019, coronavirus, vaccination, pandemic, SARS-COV-2 infection, antiviral activity, severe acute respiratory syndrome Coronavirus, sofosbuvir, SARS-CoV-2 vaccine, RNA, Protease inhibitor, Health, human lung, hepatitis C virus, hepatitis C, VERO E6 cells, therapeutic agent, inhibitor, binding, Cytopathic effect, asunaprevir, calu-3 cells, daclatasvir, Vero E6, life cycle, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, infected cells, candidate, SARS-CoV-2 propagation, SARS-CoV-2-infected cells, viral life cycle, protein level, cytopathic effects, virion, protein levels, NS5A, RNA polymerase inhibitor, direct-acting antiviral, human lung Calu-3 cells, blocked, significantly, include, evaluated, inhibited, 【제목키워드】 potent, asunaprevir, Propagation, block,