SARS-CoV-2 epidemics quickly propagated worldwide, sorting virus genomic variants in newly established propagules of infections. Stochasticity in transmission within and between countries or an actual selective advantage could explain the global high frequency reached by some genomic variants. Using statistical analyses, demographic reconstructions, and molecular dynamics simulations, we show that the globally invasive G614 spike variant i) underwent a significant demographic expansion in most countries not explained by stochastic effects nor by overrepresentation in clinical samples; ii) increases the spike S1/S2 furin-like site conformational plasticity (short-range effect), and iii) modifies the internal motion of the receptor-binding domain affecting its cross-connection with other functional domains (long-range effect). Our results support the hypothesis of a selective advantage at the basis of the spread of the G614 variant, which we suggest may be due to structural modification of the spike protein at the S1/S2 proteolytic site, and provides structural information to guide the design of variant-specific drugs.

中文翻译：

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短期和长期的群体动态和结构效应支持 G614 SARS-Cov2 尖峰变体的选择性优势的假设

SARS-CoV-2 流行病在全球范围内迅速传播，在新建立的感染繁殖体中对病毒基因组变异进行分类。国家内部和国家之间传播的随机性或实际的选择优势可以解释某些基因组变异在全球范围内出现的高频率。通过统计分析、人口统计重建和分子动力学模拟，我们表明全球侵入性 G614 尖峰变体i)在大多数国家经历了显着的人口扩张，这不能用随机效应或临床样本中的过度代表性来解释；ii)增加尖峰 S1/S2 弗林蛋白酶样位点的构象可塑性（短程效应），以及iii)改变受体结合结构域的内部运动，影响其与其他功能域的交叉连接（长程效应）。我们的结果支持基于 G614 变体传播的选择性优势的假设，我们认为这可能是由于 S1/S2 蛋白水解位点处刺突蛋白的结构修饰所致，并提供了结构信息来指导 G614 变体的设计变异特异性药物。