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, A minha amada mãe, que sempre me apoiou e incentivou a seguir meus sonhos, esta vitória também é sua. A minha amada Vó Leda que mesmo distante sempre se preocupou comigo. E ao meu padrasto Cássio Rocha por sempre me prestar auxílio. Aos meus amados avós, Rita e José Pedro e, tias, Marluce, Marlene e Jandira que sempre foram atenciosas comigo em toda a trajetória do mestrado. Ao meu orientador e professor Rodrigo Guerino Stabeli, que depositou em mim sua confiança, me aceitando como seu primeiro aluno em Ribeirão Preto. Agradeço aos ensinamentos que me proporcionou ao longo desses dois anos. Aos professores e funcionários do programa de Pós-Graduação em Imunologia Básica e Aplicada da FMRP, em especial à Ana Cristina, que sempre esteve presente e solícita nos momentos de necessidade. Ao meu amigo Rafael Pontes, que desde a graduação acompanha meus passos na carreira acadêmica, obrigado por todo apoio e consideração. As minhas amigas Caroline Galvão e Jéssica Placência, que mesmo distante fisicamente, sempre estiveram presentes na minha vida.
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