Affiliation:
1. Department of Microbiology, MS Ramaiah College of Arts, Science and Commerce, Bangalore, 560054, India
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.
Funder
Karnataka State Council for Science and Technology
Gokula Education Foundation, Bengaluru, India
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Molecular Medicine,General Medicine
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献