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对 SARS-CoV-2 刺突糖蛋白的进化和密码子使用偏好的深入了解。

Evolutionary and codon usage preference insights into spike glycoprotein of SARS-CoV-2.

机构信息

College of Animal Biotechnology, GADVASU, Ludhiana.

Aligarh Muslim University India.

出版信息

Brief Bioinform. 2021 Mar 22;22(2):1006-1022. doi: 10.1093/bib/bbaa383.

Abstract

Interaction of SARS-CoV-2 spike glycoprotein with the ACE2 cell receptor is very crucial for virus attachment to human cells. Selected mutations in SARS-CoV-2 S-protein are reported to strengthen its binding affinity to mammalian ACE2. The N501T mutation in SARS-CoV-2-CTD furnishes better support to hotspot 353 in comparison with SARS-CoV and shows higher affinity for receptor binding. Recombination analysis exhibited higher recombination events in SARS-CoV-2 strains, irrespective of their geographical origin or hosts. Investigation further supports a common origin among SARS-CoV-2 and its predecessors, SARS-CoV and bat-SARS-like-CoV. The recombination events suggest a constant exchange of genetic material among the co-infecting viruses in possible reservoirs and human hosts before SARS-CoV-2 emerged. Furthermore, a comprehensive analysis of codon usage bias (CUB) in SARS-CoV-2 revealed significant CUB among the S-genes of different beta-coronaviruses governed majorly by natural selection and mutation pressure. Various indices of codon usage of S-genes helped in quantifying its adaptability in other animal hosts. These findings might help in identifying potential experimental animal models for investigating pathogenicity for drugs and vaccine development experiments.

摘要

SARS-CoV-2 刺突糖蛋白与 ACE2 细胞受体的相互作用对于病毒附着到人类细胞非常关键。据报道,SARS-CoV-2 S 蛋白中的某些突变会增强其与哺乳动物 ACE2 的结合亲和力。与 SARS-CoV 相比,SARS-CoV-2 CTD 中的 N501T 突变为热点 353 提供了更好的支持,并显示出更高的受体结合亲和力。重组分析表明,SARS-CoV-2 株发生了更高的重组事件,无论其地理来源或宿主如何。研究进一步支持了 SARS-CoV-2 与其前体 SARS-CoV 和蝙蝠 SARS 样冠状病毒之间的共同起源。重组事件表明,在 SARS-CoV-2 出现之前,在可能的宿主和人类宿主中,共同感染的病毒之间存在遗传物质的持续交换。此外,对 SARS-CoV-2 密码子使用偏性(CUB)的综合分析表明,不同β冠状病毒的 S 基因之间存在显著的 CUB,主要由自然选择和突变压力决定。S 基因的各种密码子使用指数有助于量化其在其他动物宿主中的适应性。这些发现可能有助于确定用于研究药物和疫苗开发实验的致病性的潜在实验动物模型。

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