Structural and virologic mechanism of the emergence of resistance to M pro inhibitors in SARS-CoV-2

What is it about?

We analyzed how the COVID-19 virus main protease (SCoV2-Mpro, a viral enzyme critical for survival of the virus ) inhibitor-resistant variants emerge when the COVID-19 virus is propagated under selection pressure of an inhibitor (nirmatrelvir).

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Why is it important?

We found an amino acid substitution, which loosens the inhibitor’s binding to SCoV2-Mpro and compromises the therapeutic activity of the inhibitor. The data shed light on developing more potent agents against COVID-19 virus including drug-resistant variants.