SARS-CoV-2 3CL^pro Mutations Selected in a VSV-Based System Confer Resistance to Nirmatrelvir, Ensitrelvir, and GC376

To identify mutations that confer resistance to a protease inhibitor against protease 3CLpro, investigators 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.