Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design.
Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design.
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DOI：
10.1038/s41580-021-00432-z
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Campbell EA
中科院分区：
文献类型：
--
作者：
Malone B;Urakova N;Snijder EJ;Campbell EA
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)已导致数百万人死亡，并继续引发全球大规模动荡。冠状病毒是一种正链核糖核酸病毒，基因组大小约为30 kb。它们表达依赖于RNA的RNA聚合酶和一组其他复制酶和支持因子来转录和复制它们的基因组。执行这些基本过程的蛋白质是主要的抗病毒药物靶点，但由于我们对冠状病毒RNA合成和加工的不完全理解，药物发现受到阻碍。在受感染的细胞中，依赖于RNA的RNA聚合酶必须与其他病毒和宿主因子协调，以产生病毒mRNAs和新的基因组。最近，旨在破译和了解SARS-CoV-2复制和转录复合蛋白亚单位的结构、功能和相互作用的研究迅速发展。在这篇综述中，我们讨论了在我们对冠状病毒RNA合成机制的分子基础和复杂性的理解方面的最新进展。具体地说，我们概述了RNA翻译、复制和转录的机制和调控。我们还讨论了复制和转录复合体的组成以及它们作为抗病毒治疗靶点的适用性。严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和其他冠状病毒依赖于一组专门的病毒蛋白来转录和复制它们的RNA基因组。最近的研究提高了我们对冠状病毒RNA翻译、复制和转录的理解，并提供了新的治疗靶点。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed millions of people and continues to cause massive global upheaval. Coronaviruses are positive-strand RNA viruses with an unusually large genome of ~30 kb. They express an RNA-dependent RNA polymerase and a cohort of other replication enzymes and supporting factors to transcribe and replicate their genomes. The proteins performing these essential processes are prime antiviral drug targets, but drug discovery is hindered by our incomplete understanding of coronavirus RNA synthesis and processing. In infected cells, the RNA-dependent RNA polymerase must coordinate with other viral and host factors to produce both viral mRNAs and new genomes. Recent research aiming to decipher and contextualize the structures, functions and interplay of the subunits of the SARS-CoV-2 replication and transcription complex proteins has burgeoned. In this Review, we discuss recent advancements in our understanding of the molecular basis and complexity of the coronavirus RNA-synthesizing machinery. Specifically, we outline the mechanisms and regulation of RNA translation, replication and transcription. We also discuss the composition of the replication and transcription complexes and their suitability as targets for antiviral therapy. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses rely on a cohort of specialized viral proteins to transcribe and replicate their RNA genomes. Recent studies have improved our understanding of coronavirus RNA translation, replication and transcription, and offer new therapeutic targets.
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