Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Scand J Immunol. 2021 Oct;94(4):e13044. doi: 10.1111/sji.13044. Epub 2021 Aug 10.
Coronaviruses (CoVs) are a large family of respiratory viruses which can cause mild to moderate upper respiratory tract infections. Recently, new coronavirus named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified which is a major threat to public health. Innate immune responses play a vital role in a host's defence against viruses. Interestingly, CoVs have evolved elaborate strategies to evade the complex system of sensors and signalling molecules to suppress host immunity. SARS-CoV-2 papain-like protease (PLpro), as an important coronavirus enzyme, regulates viral spread and innate immune responses. SCoV-2 PLpro is multifunctional enzyme with deubiquitinating (DUB) and deISGylating activity. The PLpro can interact with key regulators in signalling pathways such as STING, NF-κB, cytokine production, MAPK and TGF-β and hijack those to block the immune responses. Therefore, the PLpro can be as an important target for the treatment of COVID-19. Until now, several drugs or compounds have been identified that can inhibit PLpro activity. Here we discuss about the dysregulation effects of PLpro on immune system and drugs that have potential inhibitors for SCoV-2 PLpro.
冠状病毒（CoV）是一类能够引起轻度至中度呼吸道感染的大型呼吸道病毒家族。最近，一种名为严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的新型冠状病毒已被确定，它对公众健康构成了重大威胁。先天免疫反应在宿主抵抗病毒的防御中起着至关重要的作用。有趣的是，CoV 已经进化出了精细的策略来逃避复杂的传感器和信号分子系统，以抑制宿主的免疫反应。SARS-CoV-2 木瓜蛋白酶样蛋白酶（PLpro）作为一种重要的冠状病毒酶，调节病毒的传播和先天免疫反应。SCoV-2 PLpro 是一种多功能酶，具有去泛素化（DUB）和去 ISG 基化活性。PLpro 可以与信号通路中的关键调节剂相互作用，如 STING、NF-κB、细胞因子产生、MAPK 和 TGF-β，并劫持这些调节剂来阻断免疫反应。因此，PLpro 可以作为治疗 COVID-19 的重要靶点。到目前为止，已经确定了几种可以抑制 PLpro 活性的药物或化合物。在这里，我们讨论了 PLpro 对免疫系统的失调作用，以及具有 SCoV-2 PLpro 潜在抑制剂的药物。
