Department of Cellular Biochemistry, University Medical Center Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; Research Group Structure and Function of Molecular Machines, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077 Göttingen, Germany; Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, D-37075 Göttingen, Germany.
Curr Opin Virol. 2021 Jun;48:82-90. doi: 10.1016/j.coviro.2021.03.010. Epub 2021 Apr 6.
Coronaviruses use an RNA-dependent RNA polymerase (RdRp) to replicate and express their genome. The RdRp associates with additional non-structural proteins (nsps) to form a replication-transcription complex (RTC) that carries out RNA synthesis, capping and proofreading. However, the structure of the RdRp long remained elusive, thus limiting our understanding of coronavirus genome expression and replication. Recently, the cryo-electron microscopy structure of SARS-CoV-1 RdRp was reported. Driven by the ongoing COVID-19 pandemic, structural data on the SARS-CoV-2 polymerase and associated factors has since emerged at an unprecedented pace, with more than twenty structures released to date. This review provides an overview of the currently available coronavirus RdRp structures and outlines how they have, together with functional studies, led to a molecular understanding of the viral polymerase, its interactions with accessory factors and the mechanisms by which promising antivirals may inhibit coronavirus replication.
冠状病毒利用 RNA 依赖性 RNA 聚合酶（RdRp）来复制和表达其基因组。RdRp 与其他非结构蛋白（nsps）结合，形成一个复制转录复合物（RTC），该复合物进行 RNA 合成、加帽和校对。然而，RdRp 的结构长期以来一直难以捉摸，因此限制了我们对冠状病毒基因组表达和复制的理解。最近，SARS-CoV-1 RdRp 的冷冻电镜结构被报道。受当前 COVID-19 大流行的推动，自那时以来，关于 SARS-CoV-2 聚合酶和相关因素的结构数据以前所未有的速度出现，迄今为止已经发布了二十多个结构。这篇综述概述了目前可用的冠状病毒 RdRp 结构，并概述了它们如何与功能研究一起，使人们对病毒聚合酶及其与辅助因子的相互作用以及有希望的抗病毒药物可能抑制冠状病毒复制的机制有了分子水平的理解。
