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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates

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Autor(es):
da Silva Santos, Felipe Rocha [1] ; Pacheco de Azevedo, Marcela Santiago [1] ; Bielavsky, Monica [1] ; Monteiro da Costa, Hernan Hermes [1] ; Ribeiro, Daniela Gomes [1] ; do Nascimento, Gleidson Guedes [1] ; Paz Marcondes, Gabrielle Menezes [1] ; de Castro, Beatriz Portugal [1] ; de Lima Neto, Daniel Ferreira [2, 3] ; Prudencio, Carlos Roberto [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Adolfo Lutz Inst, Ctr Immunol, Lab Immunotechnol, Sao Paulo, SP - Brazil
[2] Minist Saude, Secretaria Vigilancia Saude, Coordenacao Geral Labs Saude Publ, Brasilia, DF - Brazil
[3] Univ Estadual Campinas, Dept Bioquim, Lab Termodinam Proteinas, Campinas, SP - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS; SEP 2021.
Citações Web of Science: 0
Resumo

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 Delta Delta G values and negative Delta Delta S-Vib 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 (AU)

Processo FAPESP: 17/50333-7 - Plano de desenvolvimento institucional em pesquisa do Instituto Adolfo Lutz (PDIp)
Beneficiário:Carlos Henrique Camargo
Modalidade de apoio: Auxílio à Pesquisa - Programa Modernização de Institutos Estaduais de Pesquisa