冠状病毒 2'-O-甲基转移酶：有前途的治疗靶点。

Coronavirus 2'-O-methyltransferase: A promising therapeutic target.

机构信息

Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA; World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA.

出版信息

Virus Res. 2023 Oct 15;336:199211. doi: 10.1016/j.virusres.2023.199211. Epub 2023 Sep 4.

DOI:10.1016/j.virusres.2023.199211

PMID:37634741

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10485632/

Abstract

Coronaviruses (CoVs) have been the source of multiple epidemics and a global pandemic since the start of century, and there is an urgent need to understand CoV biology and develop better therapeutics. Here, we review the role of NSP16 in CoV replication, specifically its importance to 2'-O-methylation and CoV RNA capping. We describe the attenuation phenotypes of NSP16-mutant CoVs, the roles of MDA5 and IFITs in sensing and antagonizing viral RNA lacking 2'O methylation, and the dependence on 2'-O-methylation in other virus families. We also detail the growing body of research into targeting 2'-O-methylation for therapeutics or as a platform for live attenuated vaccines. Beyond its role in RNA capping, NSP16 may have yet uncharacterized importance to CoV replication, highlighting the need for continued studies into NSP16 functions. Understanding the full contribution of NSP16 to the replicative fitness of CoVs will better inform the development of treatments against future CoV outbreaks.

摘要

冠状病毒（CoVs）自本世纪初以来一直是多次疫情和全球大流行的源头，因此迫切需要了解 CoV 生物学并开发更好的治疗方法。在这里，我们回顾了 NSP16 在 CoV 复制中的作用，特别是其对 2'-O-甲基化和 CoV RNA 加帽的重要性。我们描述了 NSP16 突变 CoV 的减毒表型、MDA5 和 IFITs 在检测和拮抗缺乏 2'O 甲基化的病毒 RNA 中的作用，以及在其他病毒家族中对 2'-O-甲基化的依赖性。我们还详细介绍了针对 2'-O-甲基化的治疗方法或作为活减毒疫苗平台的研究进展。除了在 RNA 加帽中的作用外，NSP16 对 CoV 复制可能还有尚未确定的重要作用，这凸显了继续研究 NSP16 功能的必要性。了解 NSP16 对 CoV 复制适应性的全部贡献将更好地为未来 CoV 爆发的治疗方法的开发提供信息。