Laboratory of Immunotechnology, Center of Immunology, Adolfo Lutz Institute, São Paulo, SP, Brazil.
Coordenação-Geral de Laboratórios de Saúde Pública, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brasília, Distrito Federal, Brazil.
J Biomol Struct Dyn. 2022;40(23):13184-13189. doi: 10.1080/07391102.2021.1982775. Epub 2021 Oct 11.
Spike (S) protein has been recognized as a promising molecular target for diagnostic, vaccines and antiviral drugs development for COVID-19. In this study, we analyzed the most predominant mutations in the S protein of Brazilian isolates and predicted the effect of these amino acid alterations to protein conformation. A total of 25,924 sequences were obtained from GISAID for five regions of Brazilian territory (Midwest, North, Northeast, South, and Southeast), according to exclusion criteria. Most of the SARS-CoV-2 isolates belongs to the G clade and showed a large occurrence of D614G, N501Y and L18F substitutions. Prediction effects of these amino acid substitutions on the structure dynamics of the spike protein indicated a positive ΔΔG values and negative ΔΔS in most cases which is associated to structural stabilization and flexibility reduction of the S protein. Mutations E484K, N501Y and K417N belong to several SARS-CoV-2 variants of concern such as Alpha, Beta, Gamma and Delta, and showed high incidence among Brazilian isolates. These mutations have been described to increase RBD affinity to ACE-2 host and abolishment of RBD affinity to potent neutralizing ant-RBD. The increase in rates of infection and reinfection requires continuous genomic surveillance studies in order to characterize emerging mutations and monitor vaccine efficacy, and thus consideration structural data and dynamics in the observed phenotypes.Communicated by Ramaswamy H. Sarma.
刺突（S）蛋白已被认为是 COVID-19 诊断、疫苗和抗病毒药物开发的有前途的分子靶标。在这项研究中，我们分析了巴西分离株 S 蛋白中最主要的突变，并预测了这些氨基酸改变对蛋白质构象的影响。根据排除标准，从 GISAID 共获得了巴西五个地区（中西部、北部、东北部、南部和东南部）五个区域的 25924 个序列。大多数 SARS-CoV-2 分离株属于 G 分支，并且表现出大量 D614G、N501Y 和 L18F 取代。这些氨基酸取代对刺突蛋白结构动力学的预测影响表明，在大多数情况下，ΔΔG 值为正，ΔΔS 值为负，这与 S 蛋白结构的稳定性和柔韧性降低有关。E484K、N501Y 和 K417N 突变属于几种关注的 SARS-CoV-2 变体，如 Alpha、Beta、Gamma 和 Delta，在巴西分离株中发生率较高。这些突变已被描述为增加 RBD 与 ACE-2 宿主的亲和力，并消除 RBD 与有效中和抗 RBD 的亲和力。感染和再感染率的增加需要进行连续的基因组监测研究，以表征新出现的突变并监测疫苗的功效，因此需要考虑观察到的表型中的结构数据和动力学。由 Ramaswamy H. Sarma 传达。
