Insights into the mutation T1117I in the spike and the lineage B.1.1.389 of SARS-CoV-2 circulating in Costa Rica.
Insights into the mutation T1117I in the spike and the lineage B.1.1.389 of SARS-CoV-2 circulating in Costa Rica.
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DOI：
10.1016/j.genrep.2022.101554
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发表时间：
2022-06
期刊：
影响因子：
1.3
通讯作者：
Molina-Mora JA
中科院分区：
文献类型：
--
作者：
Molina-Mora JA
引起COVID-19大流行的SARS-CoV-2病毒的新突变和基因型已在全球范围内报告。2020年期间，在哥斯达黎加，先前确定了在穗中携带突变T1117 I的主要基因型（S：T1117 I）。为了研究这种突变对刺突功能的可能影响，即病毒的生物学，实施了基于遗传学、自然选择和协同进化模型、分子对接和表位预测的不同生物信息学管道。携带S：T1117 I的序列的同源性结果显示了一个多系群，并出现了局部谱系。在哥斯达黎加，在谱系B.1.1.389中发现突变，并认为这是积极/适应性选择的产物。在刺突蛋白的功能和更稳定的相互作用与配体（nelfinavir药物）的不同变化被发现。只有一个表位的刺突中的742被突变的影响，具有一些不同的属性，但表明在免疫应答的变化很少，对疫苗的有效性没有影响。总之，这些结果表明，2020年期间该突变对哥斯达黎加具有该基因型的病毒传播具有部分益处，尽管随着2021年初引入新谱系（后来成为主导）可能不够强。此外，这里使用的生物信息学分析可以作为一种计算机策略，最终研究SARS-CoV-2病毒和其他病原体的其他感兴趣的突变。
Emerging mutations and genotypes of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic, have been reported globally. In Costa Rica during the year 2020, a predominant genotype carrying the mutation T1117I in the spike (S:T1117I) was previously identified. To investigate the possible effects of this mutation on the function of the spike, i.e. the biology of the virus, different bioinformatic pipelines based on phylogeny, natural selection, and co-evolutionary models, molecular docking, and epitopes prediction were implemented. Results of the phylogeny of sequences carrying the S:T1117I worldwide showed a polyphyletic group, with the emergence of local lineages. In Costa Rica, the mutation is found in the lineage B.1.1.389 and it is suggested to be a product of positive/adaptive selection. Different changes in the function of the spike protein and more stable interaction with a ligand (nelfinavir drug) were found. Only one epitope out 742 in the spike was affected by the mutation, with some different properties, but suggesting scarce changes in the immune response and no influence on the vaccine effectiveness. Jointly, these results suggest a partial benefit of the mutation for the spread of the virus with this genotype during the year 2020 in Costa Rica, although possibly not strong enough with the introduction of new lineages during early 2021 which became predominant later. In addition, the bioinformatic analyses used here can be applied as an in silico strategy to eventually study other mutations of interest for the SARS-CoV-2 virus and other pathogens.
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DOI：
10.1016/s2468-2667(21)00055-4
发表时间：
2021-05
期刊：
The Lancet. Public health
影响因子：
--
作者：
Graham MS;Sudre CH;May A;Antonelli M;Murray B;Varsavsky T;Kläser K;Canas LS;Molteni E;Modat M;Drew DA;Nguyen LH;Polidori L;Selvachandran S;Hu C;Capdevila J;COVID-19 Genomics UK (COG-UK) Consortium;Hammers A;Chan AT;Wolf J;Spector TD;Steves CJ;Ourselin S
通讯作者：
Ourselin S
影响因子：
5.2
作者：
Castillo AE;Parra B;Tapia P;Lagos J;Arata L;Acevedo A;Andrade W;Leal G;Tambley C;Bustos P;Fasce R;Fernández J
通讯作者：
Fernández J
影响因子：
3.7
作者：
Gupta S;Kapoor P;Chaudhary K;Gautam A;Kumar R;Open Source Drug Discovery Consortium;Raghava GP
通讯作者：
Raghava GP
影响因子：
5.2
作者：
Mercatelli, Daniele;Giorgi, Federico M.
通讯作者：
Giorgi, Federico M.
影响因子：
10.7
作者：
Murrell, Ben;Moola, Sasha;Scheffler, Konrad
通讯作者：
Scheffler, Konrad