SARS-CoV-2 continues to cause death and illness across the world. We need both vaccines and an arsenal of antiviral drugs to combat this virus.
One drug that was recently developed to treat SARS-CoV-2 is nirmatrelvir. Nirmatrelvir targets the main protease (Mpro) of SARS-CoV-2, which it needs to replicate. This molecule binds to the active site of Mpro and permanently alters it.
A recent study by Ullrich et al. sought to test whether nirmatrelvir still works when SARS-CoV-2 accumulates mutations in its Mpro. Epidemiologists have identified many mutations in this protease, so Ullrich et al. chose a selection of the most common mutations to study. They expressed mutant copies of Mpro and measured their proteolytic activity. The mutant Mpro has similar activity to wild-type.
Next, the researchers added nirmatrelvir to the mutant Mpro and calculated its inhibitory concentration. Nirmatrelvir inhibitory concentration against the mutant Mpro was similar to the wild-type.
This encouraging result suggests that nirmatrelvir will continue to work against SARS-CoV-2 in the near future, even if the virus mutates. However, in the long term we should consider developing drug cocktails to prevent resistance from evolving.
Ullrich S, Ekanayake KB, Otting G, Nitsche C. Main protease mutants of SARS-CoV-2 variants remain susceptible to nirmatrelvir. Bioorg Med Chem Lett. 2022 Apr 15;62:128629. doi.org/10.1016/j.bmcl.2022.128629. PMID: 35182772