Coronaviruses are a diverse subfamily of viruses containing pathogens of humans and animals. This subfamily of viruses replicates their RNA genomes using a core polymerase complex composed of viral non-structural proteins: nsp7, nsp8 and nsp12. Most of our understanding of coronavirus molecular biology comes from betacoronaviruses like SARS-CoV and SARS-CoV-2, the latter of which is the causative agent of COVID-19. In contrast, members of the alphacoronavirus genus are relatively understudied despite their importance in human and animal health. Here we have used cryo-electron microscopy to determine structures of the alphacoronavirus porcine epidemic diarrhea virus (PEDV) core polymerase complex bound to RNA. One structure shows an unexpected nsp8 stoichiometry despite remaining bound to RNA. Biochemical analysis shows that the N-terminal extension of one nsp8 is not required for in vitro RNA synthesis for alpha- and betacoronaviruses. Our work demonstrates the importance of studying diverse coronaviruses in revealing aspects of coronavirus replication and identifying areas of conservation to be targeted by antiviral drugs.

中文翻译：

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α冠状病毒聚合酶结构揭示了保守的复制因子功能

冠状病毒是包含人类和动物病原体的多种病毒亚科。该病毒亚科使用由病毒非结构蛋白 nsp7、nsp8 和 nsp12 组成的核心聚合酶复合物复制其 RNA 基因组。我们对冠状病毒分子生物学的大部分了解来自 SARS-CoV 和 SARS-CoV-2 等 β 冠状病毒，后者是 COVID-19 的病原体。相比之下，尽管α冠状病毒属的成员对人类和动物健康很重要，但它们的研究相对较少。在这里，我们使用冷冻电子显微镜来确定与 RNA 结合的 α 冠状病毒猪流行性腹泻病毒 (PEDV) 核心聚合酶复合物的结构。尽管仍与 RNA 结合，但一种结构显示出意想不到的 nsp8 化学计量。生化分析表明，α 和 β 冠状病毒的体外 RNA 合成不需要一个 nsp8 的 N 末端延伸。我们的工作证明了研究不同冠状病毒对于揭示冠状病毒复制的各个方面和确定抗病毒药物的目标保护区域的重要性。