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关注的 202012/01 SARS-CoV-2 变异株具有约两倍的复制优势,并获得令人关注的突变。

SARS-CoV-2 Variant of Concern 202012/01 Has about Twofold Replicative Advantage and Acquires Concerning Mutations.

机构信息

Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-106 Warsaw, Poland.

Inter-Faculty Individual Studies in Mathematics and Natural Sciences, The MISMaP College, University of Warsaw, 02-097 Warsaw, Poland.

出版信息

Viruses. 2021 Mar 1;13(3):392. doi: 10.3390/v13030392.

DOI:10.3390/v13030392
PMID:33804556
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8000749/
Abstract

The novel SARS-CoV-2 Variant of Concern (VOC)-202012/01 (also known as B.1.1.7), first collected in United Kingdom on 20 September 2020, is a rapidly growing lineage that in January 2021 constituted 86% of all SARS-CoV-2 genomes sequenced in England. The VOC has been detected in 40 out of 46 countries that reported at least 50 genomes in January 2021. We have estimated that the replicative advantage of the VOC is in the range 1.83-2.18 [95% CI: 1.71-2.40] with respect to the 20A.EU1 variant that dominated in England in November 2020, and in range 1.65-1.72 [95% CI: 1.46-2.04] in Wales, Scotland, Denmark, and USA. As the VOC strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. We have estimated growth rates of expanding mutations acquired by the VOC lineage to find that the L18F substitution in spike has initiated a fast growing VOC substrain. The L18F substitution is of significance because it has been found to compromise binding of neutralizing antibodies. Of concern are immune escape mutations acquired by the VOC: E484K, F490S, S494P (in the receptor binding motif of spike) and Q677H, Q675H (in the proximity of the polybasic cleavage site at the S1/S2 boundary). These mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence.

摘要

新型关注变异株(VOC)-202012/01(也称为 B.1.1.7),最初于 2020 年 9 月 20 日在英国采集,是一个快速增长的谱系,在 2021 年 1 月,它构成了英格兰所有 SARS-CoV-2 基因组序列中 86%的比例。该 VOC 已在 46 个报告至少有 50 个基因组的国家中的 40 个国家中检测到。我们估计,相对于在 2020 年 11 月在英国占主导地位的 20A.EU1 变体,VOC 的复制优势在 1.83-2.18 [95%CI:1.71-2.40]范围内,在威尔士、苏格兰、丹麦和美国的范围内为 1.65-1.72 [95%CI:1.46-2.04]。由于 VOC 株很可能在全球范围内传播并固定下来,因此监测其分子进化非常重要。我们估计了 VOC 谱系获得的扩展突变的增长率,发现刺突中的 L18F 取代引发了快速增长的 VOC 亚系。L18F 取代具有重要意义,因为它已被发现会削弱中和抗体的结合能力。值得关注的是,VOC 获得了免疫逃逸突变:E484K、F490S、S494P(在刺突的受体结合基序中)和 Q677H、Q675H(在 S1/S2 边界处的多碱性切割位点附近)。这些突变体可能会降低现有疫苗的效率,并在感染后或疫苗诱导的血清流行率增加时扩大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/8000749/6500fd87ead9/viruses-13-00392-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/8000749/aa133ddd2056/viruses-13-00392-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/8000749/6500fd87ead9/viruses-13-00392-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/8000749/a318dd08b670/viruses-13-00392-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/8000749/2d80d2fe0bf3/viruses-13-00392-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/8000749/d4748b2b8f32/viruses-13-00392-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a12/8000749/6500fd87ead9/viruses-13-00392-g007.jpg

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