Ministry of Education Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing, China; email:
Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Annu Rev Biochem. 2022 Jun 21;91:381-401. doi: 10.1146/annurev-biochem-052521-115653.
The persistence of the coronavirus disease 2019 (COVID-19) pandemic has resulted in increasingly disruptive impacts, and it has become the most devastating challenge to global health in a century. The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants challenges the currently available therapeutics for clinical application. Nonstructural proteins (also known as replicase proteins) with versatile biological functions play central roles in viral replication and transcription inside the host cells, and they are the most conserved target proteins among the SARS-CoV-2 variants. Specifically, they constitute the replication-transcription complexes (RTCs) dominating the synthesis of viral RNA. Knowledge of themolecular mechanisms of nonstructural proteins and their assembly into RTCs will benefit the development of antivirals targeting them against existing or potentially emerging variants. In this review, we summarize current knowledge of the structures and functions of coronavirus nonstructural proteins as well as the assembly and functions of RTCs in the life cycle of the virus.
持续的 2019 冠状病毒病（COVID-19）大流行造成了日益严重的破坏，它已成为一个世纪以来对全球健康最具破坏性的挑战。严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变异株的迅速出现挑战了目前可用于临床应用的治疗方法。具有多种生物学功能的非结构蛋白（也称为复制酶蛋白）在宿主细胞内的病毒复制和转录中发挥核心作用，并且它们是 SARS-CoV-2 变异株中最保守的靶蛋白。具体而言，它们构成了主导病毒 RNA 合成的复制转录复合物（RTCs）。了解非结构蛋白的分子机制及其组装成 RTCs 将有助于开发针对现有或潜在出现的变异株的抗病毒药物。在这篇综述中，我们总结了冠状病毒非结构蛋白的结构和功能以及 RTCs 在病毒生命周期中的组装和功能的最新知识。
