SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376
Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first
protease inhibitor specifically developed against the SARS-CoV-2 protease 3CLpro that has
been licensed for clinical use. To identify mutations that confer resistance to this protease
inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a
polyprotein composed of the VSV glycoprotein (G), the SARS-CoV-2 3CLpro, and the VSV
polymerase (L). Viral replication was thus dependent on the autocatalytic processing of this …
protease inhibitor specifically developed against the SARS-CoV-2 protease 3CLpro that has
been licensed for clinical use. To identify mutations that confer resistance to this protease
inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a
polyprotein composed of the VSV glycoprotein (G), the SARS-CoV-2 3CLpro, and the VSV
polymerase (L). Viral replication was thus dependent on the autocatalytic processing of this …
[引用][C] SARS-CoV-2 3CL (pro) mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376. Sci. Transl. Med. 15, eabq7360
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