Inhibitory potential of plant-derived metabolites against Zika virus: a computational-aided approach

Abstract

BackgroundThe Zika virus (ZIKV) has caused a heavy concern all over the world because of its high infectivity and mortality rate. Still, there's no specific drug or preventive medication to treat ZIKV infection despite comprehensive analysis by the researchers. PurposeThis study was designed to demonstrate the efficacy of some plant-derived bioactive compounds against ZIKV by using both structure and ligand-based virtual screening methods. MethodsA total of 35 plant metabolites were screened on the basis of their reported pharmacological activities against ZIKV NS2B-NS3 protease (5LC0), envelope protein (5JHM), capsid protein (5YGH) and NS5 RNA-dependent RNA polymerase protein (5U04) employing a molecular docking approach. Furthermore, the ADMET properties along with structural similar drug compounds as well as the probable drug targets were also predicted for our screened four metabolites i.e., chicoric acid, luteone, reserpine and rosmarinic acid. ResultsResults showed that our four screened metabolites i.e., chicoric acid, luteone, reserpine and rosmarinic acid provide the highest binding affinity to target ZIKV proteins. The Crucial binding sites, as well as drug surface hotspots were unraveled for viral targeted protein. The analysis of ADME properties exhibited that none of the compounds had side effects that would reduce their drug-like properties. As compared, the toxicity pattern analysis has unmasked the non-toxic essence of screened drug candidates. The root-mean-square deviation (RMSD) values of ligand-macromolecule complexes were 2 Å apart envelop protein-chicoric acid, although the root-mean-square fluctuation (RMSF) values showed normal atomic fluctuations within the molecular dynamics analysis except envelop protein-chicoric acid. Most of the targets of the tested compounds lie in enzymes such as protease, hydrolase and phosphatase. Besides, the study of drug structural similarity showed several structural analogs from the drugbank such as isoformononetin (DB04202), deserpidine (DB01089) and rescinnamine (DB01180) etc. and these analogs could even be a choice to combat ZIKV. ConclusionThese results may lead to the development of effective anti-ZIKV natural medicines. Further in vivo trials are strongly recommended.