Unveiling the capability of FDA-approved drugs targeting Zika virus E protein structural domains via molecular docking, dynamic simulation and in silico screening

Zika virus (ZIKV) is a mosquito-borne flavivirus, a major global health concern, due to its association with catastrophic neurological outcomes, including adult Guillain-Barré syndrome as well as microcephaly in newborns. The disease symptoms include, but are not limited to, fever, rash, conjunctivitis, headaches, and joint pain. Despite significant health concerns associated with the virus infections, there is currently no FDA-approved drug to treat ZIKV infections. ZIKV enters the host cell through the Envelope (E) protein, which suggests its importance in the virus’s life cycle. In this study, the E protein of the ZIKV was selected as a target for finding potential drugs. As the E protein further contains three domains, namely EDI, EDII, and EDIII, which were used as potential targets. More than 2400 FDA-approved drugs were docked against each domain of the E protein of the ZIKV to find the drug with the best binding energies. The protein-ligand complex stability was further evaluated through molecular dynamics (MD) simulations. Post-simulation analysis (RMSD, RMSF, Rg and hydrogen bonding) revealed that Ponatinib is an effective drug candidate for ZIKV as it was found effective against all three domains of the E protein.