CoV-er all the bases: Structural perspectives of SARS-CoV-2 RNA synthesis.
CoV-er all the bases: Structural perspectives of SARS-CoV-2 RNA synthesis.
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DOI：
10.1016/bs.enz.2021.06.004
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Darst SA
中科院分区：
文献类型：
--
作者：
Malone B;Campbell EA;Darst SA
持续的Covid-19大流行刺激了对尼多病毒严重急性呼吸综合征冠状病毒-2 （SARS-CoV-2）生物学的研究。由于病毒RNA合成机制在病毒传播中的基本作用，人们一直关注病毒RNA合成机制。RNA合成过程的核心和必需酶，RNA依赖性RNA聚合酶（RdRp），与介导关键核酸交易的病毒编码酶一起发挥作用。其中一些酶与其他RNA病毒具有共同特征，而另一些酶则发挥奈多病毒或冠状病毒所特有的作用。RdRps已被证实是病毒病原体的靶标，许多其他核酸加工酶也是有希望的靶标。本文综述了近年来对冠状病毒RNA合成机制的研究进展。通过对这些研究的反思，我们希望强调我们知识中的剩余空白。最近与SARS-CoV-2 RNA合成相关的结构信息的冲击，结合之前的结构、遗传和生化研究，极大地提高了我们对冠状病毒如何复制和加工其基因组RNA的理解。结构生物学不仅为从分子细节上了解酶和辅因子的功能提供了蓝图，而且为药物设计和优化提供了依据。世界各地研究人员的共同努力，再加上了解这一致命病毒家族的新紧迫性，最终可能会产生新的和改进的抗病毒药物，从而缓解当前的全球破坏。
The ongoing Covid-19 pandemic has spurred research in the biology of the nidovirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Much focus has been on the viral RNA synthesis machinery due to its fundamental role in viral propagation. The central and essential enzyme of the RNA synthesis process, the RNA-dependent RNA polymerase (RdRp), functions in conjunction with a coterie of viral-encoded enzymes that mediate crucial nucleic acid transactions. Some of these enzymes share common features with other RNA viruses, while others play roles unique to nidoviruses or CoVs. The RdRps are proven targets for viral pathogens, and many of the other nucleic acid processing enzymes are promising targets. The purpose of this review is to summarize recent advances in our understanding of the mechanisms of RNA synthesis in CoVs. By reflecting on these studies, we hope to emphasize the remaining gaps in our knowledge. The recent onslaught of structural information related to SARS-CoV-2 RNA synthesis, in combination with previous structural, genetic and biochemical studies, have vastly improved our understanding of how CoVs replicate and process their genomic RNA. Structural biology not only provides a blueprint for understanding the function of the enzymes and cofactors in molecular detail, but also provides a basis for drug design and optimization. The concerted efforts of researchers around the world, in combination with the renewed urgency toward understanding this deadly family of viruses, may eventually yield new and improved antivirals that provide relief to the current global devastation.
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