tetano
Editor, Senior Moderator
J Med Virol
. 2020 Sep 9.
doi: 10.1002/jmv.26497. Online ahead of print.
The Emerging SARS-CoV-2 Papain-like Protease: Its Relationship with Recent Coronavirus Epidemics
Mahmoud Kandeel[SUP] 1 2 [/SUP], Yukio Kitade[SUP] 3 4 [/SUP], Mahmoud Fayez[SUP] 5 6 [/SUP], Katharigata N Venugopala[SUP] 7 8 [/SUP], Abdelazim Ibrahim[SUP] 9 10 [/SUP]
Affiliations
Abstract
Background: The papain-like protease (PL[SUP]pro[/SUP] ) 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[SUP]pro[/SUP] indicates the catalytic activity of viral PL[SUP]pro[/SUP] and its interactions with ubiquitin.
Methods: By using sequence comparisons, molecular models and protein-protein interaction maps, PL[SUP]pro[/SUP] was compared in the three recorded fatal CoV epidemics, which involved SARS-CoV-2, SARS-CoV and MERS-CoV.
Results: The pairwise sequence comparison of SARS-CoV-2 PL[SUP]pro[/SUP] indicated similarity percentages of 82.59% and 30.06% with SARS-CoV PL[SUP]pro[/SUP] and MERS-CoV PL[SUP]pro[/SUP] , respectively. In comparison with SARS-CoV PL[SUP]pro[/SUP] , in SARS-CoV-2, the PL[SUP]pro[/SUP] 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[SUP]pro[/SUP] . These features might contribute to a similar or slightly lower level of deubiquitinating activity in SARS-CoV-2 PL[SUP]pro[/SUP] . It was, however, a much higher level compared to MERS-CoV, which contained amino acid mutations and a low number of polar interfaces.
Conclusion: SARS-CoV-2 PL[SUP]pro[/SUP] and SARS-CoV PL[SUP]pro[/SUP] 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. This article is protected by copyright. All rights reserved.
Keywords: COVID-19; SARS-CoV-2; innate immunity; molecular modeling; papain-like protease.
. 2020 Sep 9.
doi: 10.1002/jmv.26497. Online ahead of print.
The Emerging SARS-CoV-2 Papain-like Protease: Its Relationship with Recent Coronavirus Epidemics
Mahmoud Kandeel[SUP] 1 2 [/SUP], Yukio Kitade[SUP] 3 4 [/SUP], Mahmoud Fayez[SUP] 5 6 [/SUP], Katharigata N Venugopala[SUP] 7 8 [/SUP], Abdelazim Ibrahim[SUP] 9 10 [/SUP]
Affiliations
- PMID: 32902889
- DOI: 10.1002/jmv.26497
Abstract
Background: The papain-like protease (PL[SUP]pro[/SUP] ) 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[SUP]pro[/SUP] indicates the catalytic activity of viral PL[SUP]pro[/SUP] and its interactions with ubiquitin.
Methods: By using sequence comparisons, molecular models and protein-protein interaction maps, PL[SUP]pro[/SUP] was compared in the three recorded fatal CoV epidemics, which involved SARS-CoV-2, SARS-CoV and MERS-CoV.
Results: The pairwise sequence comparison of SARS-CoV-2 PL[SUP]pro[/SUP] indicated similarity percentages of 82.59% and 30.06% with SARS-CoV PL[SUP]pro[/SUP] and MERS-CoV PL[SUP]pro[/SUP] , respectively. In comparison with SARS-CoV PL[SUP]pro[/SUP] , in SARS-CoV-2, the PL[SUP]pro[/SUP] 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[SUP]pro[/SUP] . These features might contribute to a similar or slightly lower level of deubiquitinating activity in SARS-CoV-2 PL[SUP]pro[/SUP] . It was, however, a much higher level compared to MERS-CoV, which contained amino acid mutations and a low number of polar interfaces.
Conclusion: SARS-CoV-2 PL[SUP]pro[/SUP] and SARS-CoV PL[SUP]pro[/SUP] 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. This article is protected by copyright. All rights reserved.
Keywords: COVID-19; SARS-CoV-2; innate immunity; molecular modeling; papain-like protease.