Biolegend, 795406, Recombinant SARS-CoV-2 3C-Like Main Protease

SARS CoV-2 3C-like main protease (3CLpro) is one of the two cysteine proteases that process the viral polyproteins of the SARS-CoV-2 virus responsible for the disease known as COVID-19 (1). Polyproteins pp1a and pp1ab are cleaved by 3CLpro and papain-like protease (PLpro) to produce 16 putative non-structural proteins. This proteolytic cleavage step is essential for viral replication and infection. 3CLpro is homodimeric in its active form and inactive as a monomer (2). The active form recognizes and cleaves the recognition sequence Leu-Gln↓(Ser/Ala/Gly). Domains I and II of 3CLpro consists of two β-barrel domains that form the chymotrypsin structure, and domain III contains a Cys-His catalytic dyad. The substrate binding site can be found in a cleft between domains I and II. 3CLpro, PLpro, and ACE2 currently serve as major therapeutic drug targets. There exists a variety of inhibitors of other coronavirus 3C-like proteases that may be considered for their antiviral potential against the novel coronavirus (3). These include small molecule inhibitors as well as larger molecules that mimic the recognition peptide structure. Inhibitors of the HIV Asp protease have been shown to treat SARS infection and are theorized to be effective inhibitors of 3CLpro (4). Some broad spectrum 3CLpro inhibitors have been shown to be effective against the SARS-CoV-2 in vitro (5).