Atividade antiviral de toxinas de serpente bothrops jararacussu no ciclo replicativo do zika vírus

Abstract

Zika virus (ZIKV) is the etiologic agent of Zika fever, a globally spreading mosquito-borne infection, previously associated with cases of microcephaly. Potential new outbreaks of ZIKV are priority problems for the governments since arboviruses are infections that are easily spread in tropical regions such as Brazil. According to the Ministry of Health, ZIKV represents a worldwide public health problem, resulting in social, economic, and public health system (SUS) significant impacts, since there is no effective antiviral treatment and licensed vaccines. In this context, natural compounds have several biological reported activities, such as antioxidant, antiparasitic, antibacterial, and antiviral, as well as toxins isolated from the venom of snakes have shown activity against several viruses. Here the anti-ZIKV activity of Bothropstoxins-I and II (BthTX-I and II) isolated from Bothrops jararacussu venom was investigated. Vero E6 cells were infected with ZIKVPE243 in the presence of compounds for 72 hours, when virus titers were quantified. The results demonstrated that BthTX-I and II presented strong dose-dependent inhibition, with a selective index of 149.1 and 1.44 x 105, respectively. These toxins mainly inhibited the early stages of the replicative cycle, such as during the entry of ZIKV into host cells, as shown by the potent virucidal effect, suggesting the action of these toxins on the virus particles. Moreover, BthTX-I and II presented significant activity towards the post‑entry stages of the ZIKV replicative cycle. Molecular docking analyses showed that BthTX-I and II potentially interact with ZIKV Envelope protein through hydrogen bonds and hydrophobic interactions. Our findings show that these toxins could be used as useful templates for the development of future antiviral candidate drugs against Zika fever.