Integrated chemoinformatics-molecular docking approach to drug discovery against viruses

Document Type



Biological and Biomedical Sciences


Background: In the current study, we have used an integrated in silico approach that combines chemoinformatics and molecular docking to screen and test potential therapeutic compounds against viruses in a computer-simulated environment. Fluoroquinolones have been shown to inhibit HCV replication by targeting the helicase activity of HCV NS3. Based on this observation, we hypothesized that natural analogs of fluoroquinolones will have similar or superior inhibitory potential, while having potentially fewer adverse effects.
Methods: To screen for natural analogs of fluoroquinolones, we devised an integrated in silico Chemoinformatics-Molecular Docking approach. Using the structural features of 17 fluoroquinolones as bait reference, we screened large databases of natural analogs. 10399 natural compounds and their derivatives were retrieved from the databases. From these compounds, molecules bearing physicochemical similarities with fluoroquinolones were screened using a chemoinformatics approach.
Results: Twenty compounds were picked up in this screening. These compounds were then docked on the structure of HCV NS3 helicase to analyze mutual interactions of the two molecules. Results from the molecular docking analysis showed 32 amino acids in the HCV NS3 active site that were most frequently targeted by fluoroquinolones as well as by their natural analogues, indicating a functional similarity between the two groups of compounds.
Conclusion: This study describes a speedy and inexpensive approach to complement drug discovery and design. The in silico analyses we used here can be employed to short-list promising compounds prior to their testing in wet-lab. This will tremendously economize on time and money spent on the screening of putative drugs.


Volume, Issue and Pagination are not provided by the author/publisher

Publication (Name of Journal)

Infectious Disorders Drug Targets