Title:In silico Analysis of Natural Inhibitors against HPV E6 Protein
Volume: 20
Issue: 3
Author(s): Vemula Vani, Snehalatha Venkateshappa, Rachel Nishitha, Hima Shashidhar, Arpitha B. Hegde and Manikandan Alagumuthu*
Affiliation:
- Department of Microbiology, MS Ramaiah College of Arts, Science and Commerce, Bangalore, 560054, India
Keywords:
ADME, anti-cervical cancer, HPV16 E6, natural products, small molecule inhibitors, molecular dynamics simulations.
Abstract:
Background: Drug re-purposing is one of the cost-effective methods to establish novel
therapeutics against many diseases. Established natural products are collected from databases and
used to potentially screen them against HPV E6 protein, a critical viral protein.
Objective: This study aims to design potential small molecule inhibitors against HPV E6 protein
using structure-based approaches. Ten natural anti-cancerous compounds (Apigenin, Baicalein,
Baicalin, Ponicidin, Oridonin, Lovastatin, Triterpenoid, Narirutin, Rosmarinic Acid, and Xanthone)
were selected by review of the literature.
Methods: These compounds were screened using Lipinski Rule of Five. Out of ten compounds,
seven were found to satisfy Rule of five. Docking of these seven compounds was carried out using
AutoDock software and corresponding Molecular Dynamics Simulations were performed by
GROMACS.
Results: Among the seven compounds docked with the E6 target protein, six compounds showed
lesser binding energy than the reference compound, Luteolin. The three-dimensional structures
of E6 protein and the corresponding ligand complexes were visualised and analysed using PyMOL
whereas the two-dimensional images of protein-ligand interactions were obtained by LigPlot+
software to study the specific interactions. ADME analysis using SwissADME software revealed
that all the compounds except Rosmarinic acid have good gastrointestinal absorption
and solubility characteristics while Xanthone and Lovastatin showed blood brain barrier
penetration properties. Considering the binding energy and ADME analysis, Apigenin and
Ponicidin are found to be most suitable for de novo designing of potential inhibitors against the
HPV16 E6 protein.
Conclusion: Further, synthesis and characterization of these potential HPV16 E6 inhibitors will
be carried out and their functional evaluation using cell culture-based assays will be undertaken.
