Desenvolvimento de compostos ativos contra os vírus dengue e Zika: um combate às doenças negligenciadas

Abstract

Zika fever, a neglected tropical disease (NTD), caused by the Zika virus (ZIKV), which is a Flavivirus belonging to the Flaviviridae family, is mainly transmitted by the bite of infected mosquitoes of the Aedes aegypti and Ae. species albopictus, during the blood meal. In Brazil, a total of 1.3 million individuals were infected in 2016 and in the State of Alagoas, 393 cases of Zika were documented in 2019. Of these, 32 cases were reported in pregnant patients. In these cases, ZIKV can lead to an increased rate of microcephaly in newborns. In the first months of 2024, around 2 million cases of dengue were documented, including 16.494 cases of severe dengue and more than 600 confirmed deaths (COE). Considering such information, it becomes extremely important to research new chemical compounds with potential antiviral activity against these viruses. In the PIBIC cycle (2020-2022), our research group was able to identify four new NS2B/NS3 inhibitors (Ki = 7-15 µM), beloging to the cyanoacrylamide class, being the first inhibitors of this class capable of acting competitively on such a targetAs all derivatives are equipotent and present the same types of interactions with ZIKV NS2B/NS3, the LQM471 derivative was selected as a prototype for such modifications, where two regions of the molecule were explored. Thus, two new series of synthesized compounds were properly characterized by spectroscopic and spectrometric techniques.