Contribution of single mutations to selected SARS-CoV-2 emerging variants spike antigenicity.

Contribution of single mutations to selected SARS-CoV-2 emerging variants spike antigenicity.
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DOI:
10.1016/j.virol.2021.09.001
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发表时间:
2021-11
期刊:
影响因子:
3.7
通讯作者:
Finzi A
Finzi A
中科院分区:
医学3区
文献类型:
--
作者:
Gong SY;Chatterjee D;Richard J;Prévost J;Tauzin A;Gasser R;Bo Y;Vézina D;Goyette G;Gendron-Lepage G;Medjahed H;Roger M;Côté M;Finzi A

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到 2020 年底,原始 SARS-CoV-2 武汉-Hu-1 毒株已出现多种关注变体 (VOC) 和感兴趣变体 (VOIs)。刺突蛋白的突变因其对传播性、发病机制和疫苗功效的影响而受到严格审查。在这里,我们通过评估单个突变对选定变体的整体抗原性及其与 ACE2 受体结合的影响,为不断增长的关于新兴变体的文献做出贡献。我们观察到单个突变体对与 ACE2 相互作用和抗原性相关的全局变异表型的不同贡献。使用生物层干涉测量法,我们观察到 ACE2 相互作用的增强主要是通过解离速率的降低来调节的。最后,我们进行了有趣的观察,与 D614G 变体相比,测试的新兴变体的 Spike 在 37°C 下与 ACE2 的结合更好。较高温度下改善的 ACE2 结合是否有利于新兴变异的传播仍有待证明。
Towards the end of 2020, multiple variants of concern (VOCs) and variants of interest (VOIs) have arisen from the original SARS-CoV-2 Wuhan-Hu-1 strain. Mutations in the Spike protein are highly scrutinized for their impact on transmissibility, pathogenesis and vaccine efficacy. Here, we contribute to the growing body of literature on emerging variants by evaluating the impact of single mutations on the overall antigenicity of selected variants and their binding to the ACE2 receptor. We observe a differential contribution of single mutants to the global variants phenotype related to ACE2 interaction and antigenicity. Using biolayer interferometry, we observe that enhanced ACE2 interaction is mostly modulated by a decrease in off-rate. Finally, we made the interesting observation that the Spikes from tested emerging variants bind better to ACE2 at 37°C compared to the D614G variant. Whether improved ACE2 binding at higher temperature facilitates emerging variants transmission remain to be demonstrated.
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