Ellagic Acid as a Potential Inhibitor against the Nonstructural Protein NS3 Helicase of Zika Virus: A Molecular Modelling Study

Abstract

Zika virus is a member of the Flaviviridae family and genus Flavivirus, which has a phylogenetic relationship with spondweni virus. It spreads to humans through a mosquito bite. To identify potential inhibitors for the Zika virus with biosafety, we selected natural antiviral compounds isolated from plant sources and screened against NS3 helicase of the Zika virus. The enzymatic activity of the NS3 helicase is associated with the C-terminal region and is concerned with RNA synthesis and genome replication. It serves as a crucial target for the Zika virus. We carried out molecular docking for the target NS3 helicase against the selected 25 phytochemicals using AutoDock Vina software. Among the 25 plant compounds, we identified NS3 helicase-ellagic acid (-9.9 kcal/mol), NS3 helicase-hypericin (-9.8 kcal/mol), and NS3 helicase-pentagalloylglucose (-9.5 kcal/mol) as the best binding affinity compounds based on their binding energies. To understand the stability of these complexes, molecular dynamic simulations were executed and the trajectory analysis exposed that the NS3 helicase-ellagic acid complex possesses greater stability than the other two complexes such as NS3 helicase-hypericin and NS3 helicase-pentagalloylglucose. The ADMET property prediction of these compounds resulted in nontoxicity and noncarcinogenicity.

Herb Robert’s Gift against Human Diseases: Anticancer and Antimicrobial Activity of Geranium robertianum L.

“…The ellagic acid inhibited human rhinoviruses HRV-2, -3, and -4, with higher activity than ribavirin used as a control antiviral drug [ 29 ]. Recently, ellagic acid was identified as a potential inhibitor of NS3 helicase of the Zika virus, an arbovirus belonging to the Flaviviridae family [ 30 , 31 ]. Cui et al [ 32 ] reported that ellagic acid and gallic acid exert antiviral activity against the Ebola virus by inhibiting virus entry into the cell.…”

Interactions and mechanisms of phenolic compounds with human immunodeficiency virus-1 Tat protein

“…Structurally, presents four rings representing the lipophilic domain, four phenolic groups, and two lactones, which form hydrogen-bonds sides and act as electron acceptors respectively, and that represents the hydrophilic domain [32]. In addition, ellagic acid has been reported to possess antiviral activity demonstrated by in vitro models [33]. Moreover, in an in vitro study, it was reported that of the identified specialized metabolites in Punica granatum (Pomegranate), ellagic acid was one of the compounds that exhibited the most relevant inhibition of HIV-1 RT-associated ribonuclease H (RNase H) and HIV-1 integrase (IN) lens epithelium-derived growth factor (LEDGF)-dependent activities [34].…”