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

智利亚南极地区 SARS-CoV-2 单倍型突变揭示了新冠病毒刺突动态的新见解

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

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.

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