The emerging SARS‐CoV‐2 papain‐like protease: Its relationship with recent coronavirus epidemics

Abstract

The papain-like protease (PL^pro ) is an important enzyme for coronavirus polyprotein processing, as well as for virus-host immune suppression. Previous studies reveal that a molecular analysis of PL^pro indicates the catalytic activity of viral PL^pro and its interactions with ubiquitin. By using sequence comparisons, molecular models, and protein-protein interaction maps, PL^pro was compared in the three recorded fatal CoV epidemics, which involved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe acute respiratory syndrome CoV (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV). The pairwise sequence comparison of SARS-CoV-2 PL^pro indicated similarity percentages of 82.59% and 30.06% with SARS-CoV PL^pro and MERS-CoV PL^pro , respectively. In comparison with SARS-CoV PL^pro , in SARS-CoV-2, the PL^pro had a conserved catalytic triad of C111, H278, and D293, with a slightly lower number of polar interface residues and of hydrogen bonds, a higher number of buried interface sizes, and a lower number of residues that interact with ubiquitin and PL^pro . These features might contribute to a similar or slightly lower level of deubiquitinating activity in SARS-CoV-2 PLpro. It was, however, a much higher level compared to MERS-CoV, which contained amino acid mutations and a low number of polar interfaces. SARS-CoV-2 PL^pro and SARS-CoV PL^pro showed almost the same catalytic site profiles, interface area compositions and polarities, suggesting a general similarity in deubiquitination activity. Compared with MERS-CoV, SARS-CoV-2 had a higher potential for binding interactions with ubiquitin. These estimated parameters contribute to the knowledge gap in understanding how the new virus interacts with the immune system.