Inhibitors Targeting SARS-CoV-2 Viral Protein Show Strong Antiviral Activity in Transgenic Mouse Model

Drug-approved inhibitors designed to disrupt the viral SARS-CoV-2 Mpro protein exhibit strong antiviral activity both in vitro and in a transgenic mouse model, according to a new study. While vaccines are an important tool in the fight against COVID-19, the development of antiviral drugs remains a high priority, especially with the rise of variants that may partially escape vaccines.

The Mpro viral protein is a protease required to cleave precursor polyproteins into functional viral proteins. This essential function makes it a key drug target. Jingxin Qiao et al. have developed 32 boceprivir or teleprovir-based inhibitors, both of which are protease inhibitors approved to treat hepatitis C virus.

Six compounds protected cells from viral infection with high potency and two of them were selected for in vivo studies based on pharmacokinetic experiments. In a transgenic mouse model infected with SARS-CoV-2, treatment with the two compounds dramatically reduced lung viral loads and lung damage.

Both also showed good pharmacokinetic properties and good safety in rats. The work of this article “represents an important step towards the development of anti-SARS-CoV-2 drugs available orally,” say the authors.