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Omicron (B.1.1.529) - A new heavily mutated variant: Mapped location and probable properties of its mutations with an emphasis on S-glycoprotein
International Journal of Biological Macromolecules ( IF 8.2 ) Pub Date : 2022-08-08 , DOI: 10.1016/j.ijbiomac.2022.07.254
Chiranjib Chakraborty 1 , Manojit Bhattacharya 2 , Ashish Ranjan Sharma 3 , Bidyut Mallik 4
Affiliation  

Omicron, another SARS-CoV-2 variant, has been recorded and reported as a VoC. It has already spread across >30 countries and is a highly mutated variant. We tried to understand the role of mutations in the investigated variants by comparison with previous characterized VoC. We have mapped the mutations in Omicron S-glycoprotein's secondary and tertiary structure landscape using bioinformatics tools and statistical software and developed different models. In addition, we analyzed the effect of diverse mutations in antibody binding regions of the S-glycoprotein on the binding affinity of the investigated antibodies. This study has chosen eight significant mutations in Omicron (D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H G496S), and seven of them are located in the RBD region. We also performed a comparative analysis of the ΔΔG score of these mutations to understand the stabilizing or destabilizing properties of the investigated mutations. The analysis outcome shows that D614G, Q493K, and S477N mutations are stable mutations with ΔΔG scores of 0.351 kcal/mol, 0.470 kcal/mol, and 0.628 kcal/mol, respectively, according to DynaMut estimations. While other mutations (E484A, N501Y, K417N, Y505H, G496S) showed destabilizing results. The D614G, E484A, N501Y, K417N, Y505H, and G496S mutations increased the molecular flexibility of S-glycoprotein to interact with the ACE2 receptor, increasing the variant's infectivity. Our study will contribute to research on the SARS-CoV-2 variant, Omicron, by providing information on the mutational pattern and exciting properties of these eight significant mutations, such as antibody escape and infectivity quotient (stabilizing or destabilizing; increased or decreased molecular flexibility of S-glycoprotein to interact with the human ACE2 receptor).



中文翻译:

Omicron (B.1.1.529) - 一种新的重度突变变体:映射位置和其突变的可能特性,重点是 S-糖蛋白

Omicron 是另一种 SARS-CoV-2 变体,已被记录并报告为 VoC。它已经遍布超过 30 个国家,并且是一种高度变异的变体。我们试图通过与先前表征的 VoC 进行比较来了解突变在所研究变体中的作用。我们使用生物信息学工具和统计软件绘制了 Omicron S-糖蛋白二级和三级结构景观中的突变,并开发了不同的模型。此外,我们分析了 S-糖蛋白的抗体结合区域的不同突变对所研究抗体的结合亲和力的影响。本研究选取了Omicron的8个显着突变(D614G、E484A、N501Y、Q493K、K417N、S477N、Y505H G496S),其中7个位于RBD区域。我们还对这些突变的 ΔΔG 评分进行了比较分析,以了解所研究突变的稳定或不稳定特性。分析结果表明,根据 DynaMut 估计,D614G、Q493K 和 S477N 突变是稳定的突变,ΔΔG 得分分别为 0.351 kcal/mol、0.470 kcal/mol 和 0.628 kcal/mol。而其他突变(E484A、N501Y、K417N、Y505H、G496S)显示出不稳定的结果。D614G、E484A、N501Y、K417N、Y505H 和 G496S 突变增加了 S-糖蛋白与 ACE2 受体相互作用的分子灵活性,从而增加了变体的感染性。我们的研究将通过提供有关这八种重要突变的突变模式和令人兴奋的特性的信息,为 SARS-CoV-2 变体 Omicron 的研究做出贡献,

更新日期:2022-08-09
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