SciPhar Editor
"Researchers have uncovered critical insights into how SARS-CoV-2 can develop resistance to the widely used COVID-19 therapeutic, nirmatrelvir"
Get the latest journal news delivered directly to your dashboard.
Researchers have uncovered critical insights into how SARS-CoV-2 can develop resistance to the widely used COVID-19 therapeutic, nirmatrelvir (1). The study explored various mutations in the virus's main protease (Mpro) and their impact on drug resistance and enzyme activity.
The research, which investigated eight essential Mpro mutations, found two common pathways for the virus to develop resistance to nirmatrelvir:
The study also examined ensitrelvir, another Mpro inhibitor, and found a similar resistance pattern. However, ensitrelvir exhibited lower resistance levels due to differences in binding compared to nirmatrelvir.
These findings highlight the need to develop next-generation Mpro inhibitors with different binding modalities to effectively combat nirmatrelvir-resistant mutants. Such drugs could offer more comprehensive treatment options for COVID-19 and help prevent the emergence of drug-resistant SARS-CoV-2 variants.
1. Duan, Y., Zhou, H., Liu, X. et al. Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir. Nature (2023). https://doi.org/10.1038/s41586-023-06609-0