The development of papain‐like protease from SARS‐CoV‐2, a potential drug target for antiviral screening: A review

The SARS‐CoV‐2 outbreak caused a global pandemic, claiming numerous lives and becoming this century’s most widespread life‐threatening disease. The virus relies on two specific enzymes to facilitate replication, 3‐chymotrypsin‐like protease (3CLPro) and papain‐like protease (PLpro). These enzymes are crucial in breaking down nonstructural polypeptides into functional proteins. PLpro with LXGG↓X recognition and cleavage sites also play a role in deubiquitylase (DUB) and delSGylase by cleaving after the double glycine residue of ubiquitin (Ub) and ISG15 as a mechanism to suppress the host’s innate immune response. Despite its important role in the viral infection cycle and the potential for drug discovery, no antivirals have been approved as PLpro inhibitors. Therefore, this review focuses on PLpro protein, its recombinant product development and purification, and its application as a protein target in drug discovery for COVID‐19 screening to develop effective COVID‐19 drugs.