Can Papain-like Protease Inhibitors Halt SARS-CoV-2 Replication?

Abstract

SARS-CoV-2 encoded papain-like protease (PLpro) harbors a labile Zn site (Cys₁₈₉-X-X-Cys₁₉₂-X _<i>n</i> -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.