Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.
Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelshikh University, Kafrelshikh, Egypt.
J Med Virol. 2021 Mar;93(3):1581-1588. doi: 10.1002/jmv.26497. Epub 2020 Sep 28.
The papain-like protease (PL ) 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 indicates the catalytic activity of viral PL and its interactions with ubiquitin. By using sequence comparisons, molecular models, and protein-protein interaction maps, PL 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 indicated similarity percentages of 82.59% and 30.06% with SARS-CoV PL and MERS-CoV PL , respectively. In comparison with SARS-CoV PL , in SARS-CoV-2, the PL 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 . 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 and SARS-CoV PL 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.
木瓜蛋白酶样蛋白酶（PL）是冠状病毒多蛋白加工的重要酶，也是病毒-宿主免疫抑制的重要酶。先前的研究表明，对 PL 的分子分析表明了病毒 PL 的催化活性及其与泛素的相互作用。通过序列比较、分子模型和蛋白质-蛋白质相互作用图谱，对涉及严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）、严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒（MERS-CoV）的三种已记录致命 CoV 流行中的 PL 进行了比较。SARS-CoV-2 PL 的成对序列比较表明，SARS-CoV PL 和 MERS-CoV PL 的相似百分比分别为 82.59%和 30.06%。与 SARS-CoV PL 相比，SARS-CoV-2 的 PL 具有保守的催化三联体 C111、H278 和 D293，极性界面残基和氢键数量略少，埋藏界面尺寸较大，与泛素和 PL 相互作用的残基数量较少。这些特征可能导致 SARS-CoV-2 PLpro 的去泛素化活性相似或略低。然而，与 MERS-CoV 相比，这一水平要高得多，MERS-CoV 含有氨基酸突变和较少的极性界面。SARS-CoV-2 PL 和 SARS-CoV PL 显示出几乎相同的催化位点图谱、界面区域组成和极性，表明去泛素化活性具有一般相似性。与 MERS-CoV 相比，SARS-CoV-2 与泛素的结合相互作用潜力更高。这些估计参数有助于了解新病毒如何与免疫系统相互作用的知识空白。
