Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating Covid-19 outbreaks.
Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating Covid-19 outbreaks.
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DOI：
10.1016/j.jinf.2021.06.001
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Chahinian H
中科院分区：
文献类型：
--
作者：
Fantini J;Yahi N;Azzaz F;Chahinian H
2019冠状病毒大流行的特点是SARS-CoV-2变异体的突然爆发，这些变异体在刺突蛋白的N-末端（NTD）和受体结合（RBD）结构域中都含有突变。本研究的目的是从基因组序列数据预测SARS-CoV-2变异体的传播性。我们使用了一个基于目标的分子模拟策略，结合了NTD和RBD的表面电位分析。我们观察到两个结构域协同作用以确保最佳的病毒粘附，这解释了为什么大多数变体在RBD和NTD中表现出伴随的突变。一些突变模式影响刺突蛋白对ACE-2的亲和力。然而，其他模式增加了阳性表面的尖峰，与脂筏神经节苷脂的病毒粘附动力学的决定性影响。基于对SARS-CoV-2变异体结构动力学的这一新观点，我们定义了一个传播性指数（T指数），该指数是根据冠状病毒与宿主细胞结合的动力学和亲和力参数计算的。T指数是每个变异体的特征，并预测其在动物和人类群体中的传播。T指数可用作健康监测策略，以预测由于出现令人担忧的变异而导致的未来COVID-19疫情。
the Covid-19 pandemic has been marked by sudden outbreaks of SARS-CoV-2 variants harboring mutations in both the N-terminal (NTD) and receptor binding (RBD) domains of the spike protein. The goal of this study was to predict the transmissibility of SARS-CoV-2 variants from genomic sequence data. we used a target-based molecular modeling strategy combined with surface potential analysis of the NTD and RBD. we observed that both domains act synergistically to ensure optimal virus adhesion, which explains why most variants exhibit concomitant mutations in the RBD and in the NTD. Some mutation patterns affect the affinity of the spike protein for ACE-2. However, other patterns increase the electropositive surface of the spike, with determinant effects on the kinetics of virus adhesion to lipid raft gangliosides. Based on this new view of the structural dynamics of SARS-CoV-2 variants, we defined an index of transmissibility (T-index) calculated from kinetic and affinity parameters of coronavirus binding to host cells. The T-index is characteristic of each variant and predictive of its dissemination in animal and human populations. the T-index can be used as a health monitoring strategy to anticipate future Covid-19 outbreaks due to the emergence of variants of concern.
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DOI：
10.1007/978-1-4939-6875-6_2
发表时间：
2017-01-01
期刊：
CHOLESTEROL HOMEOSTASIS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Di Scala, Coralie;Fantini, Jacques
通讯作者：
Fantini, Jacques
影响因子：
6.2
作者：
Fantini J;Yahi N
通讯作者：
Yahi N
影响因子：
5.4
作者：
Cilliers, T;Nhlapo, J;Morris, L
通讯作者：
Morris, L
影响因子：
64.8
作者：
Kemp SA;Collier DA;Datir RP;Ferreira IATM;Gayed S;Jahun A;Hosmillo M;Rees-Spear C;Mlcochova P;Lumb IU;Roberts DJ;Chandra A;Temperton N;CITIID-NIHR BioResource COVID-19 Collaboration;COVID-19 Genomics UK (COG-UK) Consortium;Sharrocks K;Blane E;Modis Y;Leigh KE;Briggs JAG;van Gils MJ;Smith KGC;Bradley JR;Smith C;Doffinger R;Ceron-Gutierrez L;Barcenas-Morales G;Pollock DD;Goldstein RA;Smielewska A;Skittrall JP;Gouliouris T;Goodfellow IG;Gkrania-Klotsas E;Illingworth CJR;McCoy LE;Gupta RK
通讯作者：
Gupta RK
影响因子：
4.6
作者：
Heidari A;Righetto I;Filippini F
通讯作者：
Filippini F