Prospecção, análises e design in silico de potenciais inibidores da proteína NS3 do vírus zika

Abstract

Zika virus belongs to the Flavivirus genus and is transmitted, mainly, by the Aēdēs ægypti female mosquito. Infected individuals have variable symptoms and may have neurological complications, some of which are irreversible, such as microcephaly, in cases of intrauterine infection. In addition, there are still no effective drugs for the treatment of this viral disease. However, there are still no effective drugs to treat this disease. That’s why, this work aimed to identify potential compounds with antiviral action using as a therapeutic target the Zika virus NS3 protease. Therefore, computational methods such as the construction of a shape-based model, virtual screening, covalent and non-covalent molecular docking, molecular modification and prediction of pharmacological characteristics were used. The protein and compounds tested were obtained through a virtual database of compounds, such as: natural compounds, leadlike, druglike and approved compounds (eg, drugs approved by the FDA). Through virtual screening and molecular docking, it was possible to select the compounds from each group with greater affinity to the NS3 protease: 8D, 1L, 6F and 1N. The compound identified as 6F refers to the drug Betrixaban indicating a potential repositioning of it for use against Zika virus. Compound 1N refers to Cryptomoscatone D1, present in Lauraceae Cryptocarya moschata and Lauraceae Cryptocarya mandioccana. The 8D and 1N compounds obtained the best docking and pharmacokinetic results and would be the most suitable for in vitro analysis.