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

AbstractThe papain‐like protease (PLpro) is an important enzyme for coronavirus polyprotein processing, as well as for virus‐host immune suppression. Previous studies reveal that a molecular analysis of PLpro indicates the catalytic activity of viral PLpro and its interactions with ubiquitin. By using sequence comparisons, molecular models, and protein–protein interaction maps, PLpro 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 PLpro indicated similarity percentages of 82.59% and 30.06% with SARS‐CoV PLpro and MERS‐CoV PLpro, respectively. In comparison with SARS‐CoV PLpro, in SARS‐CoV‐2, the PLpro 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 PLpro. 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 PLpro and SARS‐CoV PLpro 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.