Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
Department of Surgery, University of Florida College of Medicine, Jacksonville, FL, USA.
Biochem Biophys Res Commun. 2022 Jan 1;586:87-92. doi: 10.1016/j.bbrc.2021.11.059. Epub 2021 Nov 22.
There is an urgent need to understand the functional effects of mutations in emerging variants of SARS-CoV-2. Variants of concern (alpha, beta, gamma and delta) acquired four patterns of spike glycoprotein mutations that enhance transmissibility and immune evasion: 1) mutations in the N-terminal domain (NTD), 2) mutations in the Receptor Binding Domain (RBD), 3) mutations at interchain contacts of the spike trimer, and 4) furin cleavage site mutations. Most distinguishing mutations among variants of concern are exhibited in the NTD, localized to sites of high structural flexibility. Emerging variants of interest such as mu, lambda and C.1.2 exhibit the same patterns of mutations as variants of concern. There is a strong likelihood that SARS-CoV-2 variants will continue to emerge with mutations in these defined patterns, thus providing a basis for the development of next line antiviral drugs and vaccine candidates.
目前迫切需要了解 SARS-CoV-2 新兴变体中突变的功能影响。令人关注的变体（alpha、beta、gamma 和 delta）获得了四种增强传染性和免疫逃逸的刺突糖蛋白突变模式：1）N 端结构域（NTD）中的突变，2）受体结合域（RBD）中的突变，3）刺突三聚体链间接触处的突变，以及 4）弗林裂解位点突变。令人关注的变体中最具区别性的突变出现在 NTD 中，定位于结构高度灵活的部位。新兴的关注变体，如 mu、lambda 和 C.1.2，表现出与关注变体相同的突变模式。SARS-CoV-2 变体很有可能会继续出现这些定义明确的突变模式，从而为开发下一代抗病毒药物和疫苗候选物提供依据。
