Roles of Bothrops jararacussu toxins I and II: Antiviral findings against Zika virus

• Published in: International journal of biological macromolecules 2023-02, Vol.227, p.630-640
• Main Authors: Cassani, Natasha Marques, Santos, Igor Andrade, Grosche, Victória Riquena, Ferreira, Giulia Magalhães, Guevara-Vega, Marco, Rosa, Rafael Borges, Pena, Lindomar José, Nicolau-Junior, Nilson, Cintra, Adélia Cristina Oliveira, Mineo, Tiago Patriarca, Sabino-Silva, Robinson, Sampaio, Suely Vilela, Jardim, Ana Carolina Gomes
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antiviral Agents - pharmacology; Antiviral drugs; Bothrops - metabolism; Crotalid Venoms - metabolism; Humans; Molecular Docking Simulation; Toxins; Zika Virus; Zika Virus Infection - drug therapy
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.12.102

Zika virus is the etiologic agent of Zika fever, and has been previously associated with cases of microcephaly, drawing the attention of the health authorities worldwide. However, no vaccine or antiviral are currently available. Phospholipases A2 (PLA2) isolated from snake venoms have demonstrated antiviral activity against several viruses. Here we demonstrated the anti-ZIKV activity of bothropstoxins-I and II (BthTX-I and II) isolated from Bothrops jararacussu venom. Vero E6 cells were infected with ZIKVPE243 in the presence of compounds for 72 h, when virus titers were evaluated. BthTX-I and II presented strong dose-dependent inhibition of ZIKV, with a SI of 149.1 and 1.44 × 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 post-entry stages of the ZIKV replicative cycle. Molecular docking analyses showed that BthTX-I and II potentially interact with DII and DIII domains from ZIKV Envelope protein. Our findings show that these PLA2s could be used as useful templates for the development of future antiviral candidate drugs against Zika fever. •The bothropstoxins I and II (BthTX-I/II) strongly inhibit ZIKV in vitro.•BthTX-I/II impair the early stages of ZIKV infection.•BthTX-I/II completely blocked virus infection, mainly by a virucidal activity.•In silico binding interactions were observed between BthTX-I/II and ZIKV E protein.•ATR-FTIR analysis indicated interactions of BthTX-I/II with ZIKV proteins.