Variants of the SARS-CoV-2 virus circulating around the world have been found to be resistant to Paxlovid. The results, published in the journal Science Advances, indicate that this viral prosthesis inhibitor may soon become ineffective in treating COVID-19.

A study by the Midwest Center for Antiviral Drug Discovery (AVIDD) found that drug-resistant variants of the coronavirus have emerged several times independently in different parts of the world. In addition to resistance to the protease inhibitor nirmatrelvir, the active component of Paxlovid, scientists have shown that another set of mutations can confer resistance to enzitrelvir (Xocova), a protease inhibitor currently approved in Japan.

The study demonstrates that changing just one amino acid in the main protease of SARS-CoV-2 can seriously undermine the effectiveness of these antivirals.

However, despite the existence of naturally occurring circulating variants of SARS-CoV-2 with resistance to two different drugs, different variants of the coronavirus do not have simultaneous resistance to both protease inhibitors. This means that while one of the drugs may not work, the other is still effective.