Int J Antimicrob Agents . Effects of simeprevir on the replication of SARS-CoV-2 in vitro and in transgenic hACE2 mice

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Int J Antimicrob Agents


. 2021 Dec 17;106499.
doi: 10.1016/j.ijantimicag.2021.106499. Online ahead of print.
Effects of simeprevir on the replication of SARS-CoV-2 in vitro and in transgenic hACE2 mice


Elishiba Muturi ¹ , Wei Hong ¹ , Junhua Li ² , Wan Yang ³ , Jin He ³ , Hongping Wei ⁴ , Hang Yang ⁵



Affiliations

• PMID: 34929295
• DOI: 10.1016/j.ijantimicag.2021.106499

Abstract

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 angiotensin-converting 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 μM. 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.

Keywords: Antiviral efficacy; COVID-19; SARS-CoV-2; Simeprevir.