Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile.
Update on SARS-CoV-2 Omicron Variant of Concern and Its Peculiar Mutational Profile.
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DOI：
10.1128/spectrum.02732-21
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发表时间：
2022-04-27
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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作者：
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）的遗传多样化过程仍在进行中，最近导致出现了一种新的令人担忧的变体（VOC），定义为Omicron或B.1.1.529。Omicron VOC是迄今为止发现的最具差异性的变体，并立即引起了对其增加SARS-CoV-2传播性的潜在能力的关注，更令人担忧的是，逃避治疗和疫苗诱导的抗体。然而，Omicron VOC突变谱的明确定义仍然缺失。在此，我们提供了一个全面的定义和功能表征（在感染性和/或抗原性方面）的突变表征Omicron VOC。特别是，从GISAID数据库中检索了887，475个SARS-CoV-2 Omicron VOC全基因组序列，并用于精确定义其在不同病毒蛋白中的特定突变模式。此外，根据已发表的手稿，Omicron VOC尖峰突变的功能表征进行了详细讨论。最后，表征Omicron VOC和前四种VOC（α、β、γ和δ）的残基被映射到SARS-CoV-2刺突蛋白的三维结构上，以评估它们在不同刺突结构域中的定位。总的来说，我们的研究将有助于破译Omicron VOC突变谱，并将揭示其临床意义。考虑到Omicron VOC目前是全球主要的变体，这一点至关重要。重要性关注的Omicron变体（VOC）具有特殊的突变谱，其特征在于获得在先前鉴定的变体中很少检测到的突变或缺失，特别是在刺突糖蛋白中。这些突变主要存在于受体结合结构域，可能在增强严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染性（通过增加与ACE 2的结合亲和力）、危及治疗性和疫苗诱导抗体的刺突识别以及导致诊断检测失败方面发挥关键作用。据我们所知，这是对Omicron VOC潜在的新出现的突变及其生物学和临床意义的首次详尽描述之一。
The process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversification is still ongoing and has very recently led to the emergence of a new variant of concern (VOC), defined as Omicron or B.1.1.529. Omicron VOC is the most divergent variant identified so far and has generated immediate concern for its potential capability to increase SARS-CoV-2 transmissibility and, more worryingly, to escape therapeutic and vaccine-induced antibodies. Nevertheless, a clear definition of the Omicron VOC mutational spectrum is still missing. Herein, we provide a comprehensive definition and functional characterization (in terms of infectivity and/or antigenicity) of mutations characterizing the Omicron VOC. In particular, 887,475 SARS-CoV-2 Omicron VOC whole-genome sequences were retrieved from the GISAID database and used to precisely define its specific patterns of mutations across the different viral proteins. In addition, the functional characterization of Omicron VOC spike mutations was finely discussed according to published manuscripts. Lastly, residues characterizing the Omicron VOC and the previous four VOCs (Alpha, Beta, Gamma, and Delta) were mapped on the three-dimensional structure of the SARS-CoV-2 spike protein to assess their localization in the different spike domains. Overall, our study will assist with deciphering the Omicron VOC mutational profile and will shed more light on its clinical implications. This is critical considering that Omicron VOC is currently the predominant variant worldwide. IMPORTANCE The Omicron variant of concern (VOC) has a peculiar spectrum of mutations characterized by the acquisition of mutations or deletions rarely detected in previously identified variants, particularly in the spike glycoprotein. Such mutations, mostly residing in the receptor-binding domain, could play a pivotal role in enhancing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity (by increasing binding affinity for ACE2), jeopardizing spike recognition by therapeutic and vaccine-induced antibodies and causing diagnostic assay failure. To our knowledge, this is one of the first exhaustive descriptions of newly emerged mutations underlying the Omicron VOC and its biological and clinical implications.
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影响因子：
12.8
作者：
Kannan SR;Spratt AN;Sharma K;Chand HS;Byrareddy SN;Singh K
通讯作者：
Singh K
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
11.8
作者：
Focosi D;Novazzi F;Genoni A;Dentali F;Gasperina DD;Baj A;Maggi F
通讯作者：
Maggi F
影响因子：
4.8
作者：
Lai A;Bergna A;Menzo S;Zehender G;Caucci S;Ghisetti V;Rizzo F;Maggi F;Cerutti F;Giurato G;Weisz A;Turchi C;Bruzzone B;Ceccherini Silberstein F;Clementi N;Callegaro A;Sagradi F;Francisci D;Venanzi Rullo E;Vicenti I;Clementi M;Galli M;collaborative group SCIRE SARS-CoV-2 Italian Research Enterprise
通讯作者：
collaborative group SCIRE SARS-CoV-2 Italian Research Enterprise
影响因子：
82.9
作者：
Gruell H;Vanshylla K;Tober-Lau P;Hillus D;Schommers P;Lehmann C;Kurth F;Sander LE;Klein F
通讯作者：
Klein F