Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, 20742, USA.
Department of Physics, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
Virology. 2021 Feb;554:75-82. doi: 10.1016/j.virol.2020.12.010. Epub 2020 Dec 25.
Human population growth, climate change, and globalization are accelerating the emergence of novel pathogenic viruses. In the past two decades alone, three such members of the coronavirus family have posed serious threats, spurring intense efforts to understand their biology as a way to identify targetable vulnerabilities. Coronaviruses use a programmed -1 ribosomal frameshift (-1 PRF) mechanism to direct synthesis of their replicase proteins. This is a critical switch in their replication program that can be therapeutically targeted. Here, we discuss how nearly half a century of research into -1 PRF have provided insight into the virological importance of -1 PRF, the molecular mechanisms that drive it, and approaches that can be used to manipulate it towards therapeutic outcomes with particular emphasis on SARS-CoV-2.
人口增长、气候变化和全球化正在加速新型致病病毒的出现。仅在过去二十年中，冠状病毒家族的这三个成员就构成了严重威胁，促使人们加紧努力了解它们的生物学特性，以寻找可靶向的弱点。冠状病毒使用一种程序性 -1 核糖体移码 (-1 PRF) 机制来指导其复制酶蛋白的合成。这是其复制程序中的关键开关，可以作为治疗靶点。在这里，我们讨论了近半个世纪对 -1 PRF 的研究如何深入了解了 -1 PRF 的病毒学重要性、驱动它的分子机制以及可以用来操纵它以获得治疗结果的方法，特别强调了 SARS-CoV-2。
