The recent emergence of Zika virus (ZIKV) has affected many countries, with severe clinical manifestations such as fetal microcephaly and Guillain-Barr e syndrome. However, even though it is a major public health concern, there is no approved treatment available. Structural knowledge of the main neutralization regions of the envelope (E) protein of ZIKV and its interactions with neutralizing antibodies (nAbs) are crucial for the rational development of subunit vaccines and establishment of antibody-based interventions. In this study we screened from public data hot spot epitopes in conserved regions of ZIKV E protein that are nAbs targets. The result points to a conserved epitope located at domain II of the ZIKV E protein, namely adjacent dimer epitope, which is the ZIKV-117 and Z20 nAbs target. Although these two nAbs have been isolated from different donors, we have demonstrated, from structural and energetic details obtained by molecular dynamics of native and mutants, that hot spots residues of the epitope are the same for these nAbs, thereby indicating that they may share similar binding and neutralization mechanism. This convergence of information between these nAbs is important because both are potential targets for the development of therapies against ZIKV and only Z20 has its sequence and its complex structure with ZIKV E protein determined. Finally, these findings also contribute to existing knowledge, by fine mapping of the epitope/paratope residue pairs that are important for biotechnological development of therapies such as epitope mimetics for subunit vaccines and the rational design for antibody-based interventions against ZIKV.
De coração, agradeço, Aos meus pais, Marineide e Euclides, e aos meus irmãos, Eduardo e Natália, que sempre me apoiaram e incentivaram a seguir meus sonhos, esta conquista é nossa.Ao meu orientador e professor Rodrigo Guerino Stabeli, que depositou em mim sua confiança. Agradeço o incentivo, dedicação e os ensinamentos que me proporcionaram crescimento ao longo desses anos.Aos professores e funcionários do programa de Pós-Graduação em Imunologia Básica e Aplicada da FMRP, em especial à Ana Cristina, sempre presente e solícita.Ao meu amigo Luiz Felipe Araujo, obrigado pelo auxílio nos experimentos e pela amizade que vem desde a graduação.As minhas amigas Caroline Galvão e Jéssica Placência, que mesmo distante, sempre estiveram presentes me apoiando.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.