Investigação in silico da eficácia de fármacos antivirais na inibição da NS5 do vírus da Zika.

Abstract

Zika fever has become one of the biggest concerns in world public health and Brazil, especially after the recent discovery of its association with cases of microcephaly. Until now, there is no vaccine available for ZIKV, and the treatment is symptomatic. In a recent research was solved the three- dimensional structure of ZIKV NS RdRp X-Ray crystallography, a protein associated with RNA polymerase and important activator of the virus replication proccess, with this information, ocurred the possibility of making this enzyme a target for new drugs. In this context, theoretical-computational studies are of great value to indicate possible inhibitors for this enzyme that work as antiviral, so the article aimed to investigate the eficacy of drugs already described in the inhibition of NS5 RdRp of the Zika virus. The methodology adopted the following steps: analysis of the three-dimensional structure of the NS5 and its active site; search by potential inhibitors in the literature and databases of molecules; perform molecular docking simulations and analysis of interactions in protein-ligands and/or protein-protein complexes generated. Four parameters, considered to be important in the evaluation for the best complex of each docking, were used: The estimated inhibition constant (EIC), the Final Intermolecular Energy (FIE) and the Free Binding Energy (FBE) estimated by the program. The drugs tested were the antivirais: Acyclovir, Indinavir and Valgacyclovir. The research was successful in terms of the proposed objective and was able to identify interaction values between the drugs tested and the protein responsible for viral replication of the ZIKV NS5 RdRp.