Molecular docking and density function theory studies of compounds from Euphorbia hirta and Bacopa monnieri to zika virus structural and nonstructural proteins

Abstract

Background: Zika virus is an arbovirus belongs to the genus flavivirus and pose a serious global threat. The recent 2015 outbreak in Brazil was associated with a significant increase in microcephaly cases and other neurological complications in newborn babies and WHO declared Zika to be an international public health emergency. Currently, there is no specific treatment or Vaccine available for the Zika virus, and thus due to the unavailability of the antiviral drugs, the need for the identification of novel drugs is paramount. Materials and Methods: The compounds from two medicinal plants (Bacopa monnieri and Euphorbia hirta) were selected for the in silico molecular docking studies against the structural and nonstructural proteins of Zika virus. Quantum–chemical parameters density functional theory and absorption, distribution, metabolism, and excretion-toxicity (ADMET) was performed to identify the drug-likeliness properties. Results: Among the tested compounds, galloylquinic acid, Bacopaside III, and Bacopaside A were identified as leads against multiple targets of Zika virus. The identified compounds also exhibited desirable quantum chemical and ADMET properties. Conclusion: Hence, the compounds hampering the active site of the three different proteins playing a prime role in replication and fusion with desirable pharmacokinetic properties could be suggested for further in vitro and in vivo analysis of Zika virus. Abbreviations used: WHO: World Health Organization; DFT: Density function theory; ADMET: Absorption, distribution, metabolism, and excretion-toxicity; HBV: Hepatitis B virus; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; HSV: Herpes simplex virus; PDB: Protein data bank; OPLS: Optimized potential for liquid simulations; RMSD: Root-mean-square deviation; IFD XP: Induced fit docking extra precision; XP: Extra precision; PSA: Polar surface area; BBB: Blood brain barrier; A LogP 98: Atom-based Log P98; HOMO: Highest occupied molecular orbital; LUMO: Lowest unoccupied molecular orbital; DS V 4.0: Discovery Studio version 4.0; NS3: Nonstructural protein 3; NS1: Nonstructural protein 1