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来自智利亚南极地区的新冠病毒单倍型突变揭示了刺突蛋白动态变化的新见解。

Mutation in a SARS-CoV-2 Haplotype from Sub-Antarctic Chile Reveals New Insights into the Spike's Dynamics.

作者信息

González-Puelma Jorge, Aldridge Jacqueline, Montes de Oca Marco, Pinto Mónica, Uribe-Paredes Roberto, Fernández-Goycoolea José, Alvarez-Saravia Diego, Álvarez Hermy, Encina Gonzalo, Weitzel Thomas, Muñoz Rodrigo, Olivera-Nappa Álvaro, Pantano Sergio, Navarrete Marcelo A

机构信息

Escuela de Medicina, Universidad de Magallanes, Punta Arenas 6210427, Chile.

Centro Asistencial Docente y de Investigación, Universidad de Magallanes, Punta Arenas 6210005, Chile.

出版信息

Viruses. 2021 May 11;13(5):883. doi: 10.3390/v13050883.

DOI:10.3390/v13050883
PMID:34064904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8151058/
Abstract

The emergence of SARS-CoV-2 variants, as observed with the D614G spike protein mutant and, more recently, with B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (P.1) lineages, represent a continuous threat and might lead to strains of higher infectivity and/or virulence. We report on the occurrence of a SARS-CoV-2 haplotype with nine mutations including D614G/T307I double-mutation of the spike. This variant expanded and completely replaced previous lineages within a short period in the subantarctic Magallanes Region, southern Chile. The rapid lineage shift was accompanied by a significant increase of cases, resulting in one of the highest incidence rates worldwide. Comparative coarse-grained molecular dynamic simulations indicated that T307I and D614G belong to a previously unrecognized dynamic domain, interfering with the mobility of the receptor binding domain of the spike. The T307I mutation showed a synergistic effect with the D614G. Continuous surveillance of new mutations and molecular analyses of such variations are important tools to understand the molecular mechanisms defining infectivity and virulence of current and future SARS-CoV-2 strains.

摘要

如在D614G刺突蛋白突变体中观察到的，以及最近在B.1.1.7（501Y.V1）、B.1.351（501Y.V2）和B.1.1.28.1（P.1）谱系中观察到的，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现构成持续威胁，可能导致传染性和/或毒力更强的毒株。我们报告了一种具有九个突变的SARS-CoV-2单倍型的出现，其中包括刺突蛋白的D614G/T307I双突变。在智利南部亚南极的麦哲伦地区，这种变体在短时间内扩张并完全取代了先前的谱系。谱系的快速转变伴随着病例的显著增加，导致该地区成为全球发病率最高的地区之一。比较性粗粒度分子动力学模拟表明，T307I和D614G属于一个先前未被识别的动态结构域，干扰刺突蛋白受体结合结构域的流动性。T307I突变与D614G表现出协同效应。持续监测新突变并对这些变异进行分子分析，是了解决定当前和未来SARS-CoV-2毒株传染性和毒力分子机制的重要工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/93009450c5d1/viruses-13-00883-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/2c351fdd0650/viruses-13-00883-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/91c2d7e3c5f6/viruses-13-00883-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/0e9bc5a9a8cd/viruses-13-00883-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/5556b968a1a5/viruses-13-00883-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/93009450c5d1/viruses-13-00883-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/2c351fdd0650/viruses-13-00883-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/91c2d7e3c5f6/viruses-13-00883-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/0e9bc5a9a8cd/viruses-13-00883-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/5556b968a1a5/viruses-13-00883-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac07/8151058/93009450c5d1/viruses-13-00883-g005.jpg

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