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.

中文翻译：

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SARS-CoV-2 在细胞内的生命：复制-转录复合物的组装和功能

2019冠状病毒病（COVID-19）大流行的持续存在造成了越来越大的破坏性影响，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) 变种的迅速出现对目前临床应用的治疗方法提出了挑战。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着核心作用，它们是 SARS-CoV-2 变种中最保守的靶蛋白。具体来说，它们构成了主导病毒 RNA 合成的复制转录复合体 (RTC)。了解非结构蛋白的分子机制及其组装成 RTC 将有利于开发针对现有或潜在新兴变体的抗病毒药物。在这篇综述中，我们总结了当前关于冠状病毒非结构蛋白的结构和功能以及RTC在病毒生命周期中的组装和功能的知识。