SARS-CoV-2 is a positive-sense single-stranded RNA coronavirus. This virus can cause severe acute respiratory syndrome and spreads between people through aerosols and respiratory droplets. It broke out in early 2020, causing a massive epidemic contagious disease, called COVID-19 (Coronavirus disease 2019). The symptoms of COVID-19 are fever, cough, headache and even loss of smell and taste. Sadly, this disease has disrupted the rhythm of life for most people around the world.
Except for humans, other species, like cats, ferrets, and hamsters, are susceptible to SARS-CoV-2 as well. SARS-CoV-2 is highly contagious and deadly. Because of its high infectivity, kinds of variants have emerged, including alpha, beta, gamma delta, and omicron. Therefore, the development of inhibitors and vaccines for the virus is a vital subject.
Bofutrelvir (FB2001) is a SARS-CoV-2 main protease Mpro inhibitor.
From: Chiou WC, et al. Biochem Biophys Res Commun. 2022 Feb 5;591:130-136.
Bofutrelvir shows high efficiency for Mpro with an IC50 value of 53 nM and an EC50 value of 0.53 μM. It also has pan antiviral activity against SARS-CoV-2 and its variants with EC50 values of 0.42 μM, 0.39 μM, 0.28 μM, 0.27 μM and 0.26 μM for SARS-CoV-2, alpha variant, beta variant, delta variant and omicron variant, respectively. Bofutrelvir inhibits SARS-CoV-2 replication in Vero E6 cells in the presence of human serum (1.1-2.4 μM) even at the dose of EC50 values. Besides, Bofutrelvir exhibits an additive effect against SARS-CoV-2 in vitro when combined with treatment with Remdesivi.
In addition, in vivo, Bofutrelvir (100 and 200 mg/kg; i.p. once daily on day 0 and twice daily on day 1, 2 and 3 for 4 consecutive days) showed a dose-dependent efficacy to virus titers of infected mice lung, reducing the lung viral loads, effectively against SARS-CoV-2 delta variant infection
In conclusion, Bofutrelvir is a potent Mpro inhibitor against SARS-CoV-2 and its variants.
1. Ullrich S, et al. Bioorg Med Chem Lett. 2020 Sep 1;30(17):127377.
2. Shang W, et al. Antiviral Res. 2022 Dec;208:105450.