Background: In the current study, we present an integrated in silico cheminformaticsmolecular
docking approach to screen and test potential therapeutic compounds against viruses.
Fluoroquinolones have been shown to inhibit HCV replication by targeting HCV NS3-helicase.
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
Cheminformatics-Molecular Docking approach. We used 17 fluoroquinolones as bait reference, to
screen 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 analyzed using a cheminformatics-docking approach.
Results: From the 10399 compounds screened using our cheminformatics approach, only 20 compounds
were found to share physicochemical similarities with fluoroquinolones, while the remaining
10379 compounds were physiochemically different from fluoroquinolones. Molecular docking
analysis showed 32 amino acids in the HCV NS3 active site that were most frequently targeted by
fluoroquinolones and 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 against viral agents. The in silico analyses we used here can be employed to shortlist
promising compounds/putative drugs that can be further tested in wet-lab.