4.7 Article

Effects of simeprevir on the replication of SARS-CoV-2 in vitro and in transgenic hACE2 mice

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ELSEVIER
DOI: 10.1016/j.ijantimicag.2021.106499

关键词

SARS-CoV-2; COVID-19; Simeprevir; Antiviral efficacy

资金

  1. Youth Innovation Promotion Association CAS
  2. National Natural Science Foundation of China [32070187, 31770192]
  3. Sino-Africa Joint Research Center [151542KYSB20200010]

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The drug simeprevir has been predicted as a potential treatment for COVID-19, but experiments showed that it does not inhibit the replication of SARS-CoV-2 in vivo.
In a bid to contain the current COVID-19 (coronavirus disease 2019) pandemic, various countermeasures have been applied. To date, however, there is a lack of an effective drug for the treatment of COVID-19. Through molecular modelling studies, simeprevir, a protease inhibitor approved for the management of hepatitis C virus infection, has been predicted as a potential antiviral against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causative agent of COVID-19. Here we assessed the efficacy of simeprevir against SARS-CoV-2 both in vitro in Vero E6 cells and in vivo in a human angiotensinconverting enzyme 2 (hACE2) transgenic mouse model. The results showed that simeprevir could inhibit SARS-CoV-2 replication in Vero E6 cells with a half-maximal effective concentration (EC50) of 1.41 +/- 0.12 mu M. In a transgenic hACE2 mouse model of SARS-CoV-2 infection, intraperitoneal administration of simeprevir at 10 mg/kg/day for 3 consecutive days failed to suppress viral replication. These findings collectively imply that simeprevir does not inhibit SARS-CoV-2 in vivo and therefore do not support its application as a treatment against COVID-19 at a dosage of 10 mg/kg/day. (C) 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

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