Abstract
SARS-CoV-2 encoded papain-like protease (PLpro) harbors a labile Zn site (Cys189–X–X–Cys192–Xn–Cys224–X–Cys226) and a classic catalytic site (Cys111–His272–Asp286), which play key roles for viral replication and hence represent promising drug targets. In this Viewpoint, both sulfur-based drugs and peptides-based inhibitors may block Cys residues in the catalytic and/or Zn site of CoV-2-PLpro, leading to dysfunction of CoV-2-PLpro and thereby halting viral replication.
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