Structure based identification of potential inhibitors of NS3 protein of zika virus

Background: The re-emerging Zika virus has posed a serious threat to human health due to its association with the neurological disorders. The NS3 protein of Zika virus plays a pivotal role in the genome replication and thus may prove to be a critical target for the drug designing studies. Objective: The present study was conceptualized to analyze the crystal structure of NS3 protein of Zika virus followed by the identification of it’s potential inhibitors. Methods: Crystal structure of the NS3 protein was evaluated in detail. Docking of the NS3 protein was done with 130 different ligands including dengue virus inhibitors and their similar compounds along with some approved drugs. The drug likeliness properties were checked for non drug compounds. Results: Structural analysis of the NS3 protein revealed three important sites namely ATP-and RNA-binding sites as well as a central cavity. The selected ten ligands (ZINC05487635, ZINC0092398, ZINC13345444, 4-methoxyphenyl 4-chloro-3-nitrobenzoate, Luteolin, Ivermectin, Suramin, Dasatinib, Panduratin A, and ARDP0009) showed a higher binding affinity for the NS3 protein and good drug likeliness properties. Conclusion: These inhibitors could possibly act as potential lead molecules for future drug designing studies. Our present computational data is envisaged to be useful for gathering experimental evidences towards the development of potential therapeutic molecules against this arthropod mediated pathogen.