Exploring Secondary Metabolites Database of Apocynaceae, Menispermaceae, and Annonaceae to Select Potential Anti-HCV Compounds

Author(s): Renata P.C. Barros, Luciana Scotti, Marcus T. Scotti*.

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 11 , 2019

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Graphical Abstract:


Background: Hepatitis C is a disease that constitutes a serious global health problem, is often asymptomatic and difficult to diagnose and about 60-80% of infected patients develop chronic diseases over time. As there is no vaccine against hepatitis C virus (HCV), developing new cheap treatments is a big challenge.

Objective: The search for new drugs from natural products has been outstanding in recent years. The aim of this study was to combine structure-based and ligand-based virtual screening (VS) techniques to select potentially active molecules against four HCV target proteins from in-house secondary metabolite dataset (SistematX).

Materials and Methods: From the ChEMBL database, we selected four sets of 1199, 355, 290 and 237chemical structures with inhibitory activity against different targets of HCV to create random forest models with an accuracy value higher than 82% for cross-validation and test sets. Afterward, a ligandbased virtual screen of the entire 1848 secondary metabolites database stored in SistematX was performed. In addition, a structure-based virtual screening was also performed for the same set of secondary metabolites using molecular docking.

Results: Finally, using consensus analyses approach combining ligand-based and structure-based VS, three alkaloids were selected as potential anti-HCV compounds.

Conclusion: The selected structures are a starting point for further studies in order to develop new anti- HCV compounds based on natural products.

Keywords: Hepatitis C virus, Alkaloids, Terpenes, Ligand-based virtual screening, Structure-based virtual screening, Molecular dynamics.

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Year: 2019
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DOI: 10.2174/1568026619666190510094228
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