Maturation of SARS-CoV-2 virus requires two proteases, 3C-like protease (3CLPro) and Papain-like protease (PLPro), to cleave the large polyproteins 1a and 1ab to generate functional proteins. which is essential for genome replication and Coronavirus virion production. Both proteases are encoded by the polyproteins. 3CLPro is a cysteine protease and forms a homodimer. 3CLPro is the drug target of PF-07321332, a main component of the oral anti-Covid-19 drug Paxlovid. PLPro is also a cysteine protease that cleaves polyproteins and has deubiquitinating and deISG15ylating activities. PLPro is also a potential anti-Covid-19 drug target. The recombinant SARS-CoV-2 3C-like protease contains the catalytic domain from Ser3264-Gln3569.
