The proteases play essential roles in cutting the polyproteins into all of the functional units. The NSP5 in SARS-CoV-2 also called the main protease (Mpro), or 3C-like protease (3CLpro) mediates cleavage at eleven distinct sites to release NSP4 to NSP16 within the C-terminus of replicase polyprotein pp1a and pp1ab includes its own auto-proteolysis. The main protease is a dimer of two identical subunits that together form two active sites.

SGFRKMAFPSGKVEGCMVQVTCGTTTLNGLWLDDVVYCPRHVICTSEDMLNPNYEDLLIRKSNHNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTPKYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRPNFTIKGSFLNGSCGSVGFNIDYDCVSFCYMHHMELPTGVHAGTDLEGNFYGPFVDRQTAQAAGTDTTITVNVLAWLYAAVINGDRWFLNRFTTTLNDFNLVAMKYNYEPLTQDHVDILGPLSAQTGIAVLDMCASLKELLQNGMNGRTILGSALLEDEFTPFDVVRQCSGVTFQ

306 aa; 150 kDa