WP3 - Inhibitors of coronavirus proteases
The 5' two-thirds of the RNA genome of coronaviruses encode two large viral replicase polyproteins, pp1a and ppa1ab, which harbor the majority of protein components of the RNA-synthesizing machinery. These crucialpolyproteins are processed by two viral proteases, the papain -like protease ( PLpro in nsp3) and the main protease(Mpro, also called 3C-like protease, 3CLpro; in nsp5), to yield a total of 16 nonstructural proteins (nsps). Many of these proteins are crucial for viral RNA synthesis and genome expression, and their release from the polyprotein byproteolytic cleavage is critical for their maturation/activation (30). Therefore, inhibition of the function of PLpro and Mpro will block replication of the virus.