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Updated: Mar 19, 2026
High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Virtual screening reveals a viral-like polymerase inhibitor that complexes with the DNA polymerase of Moniliophthora
B S Andrade1,2, C S Souza3,2, G Santos1
1Departamento de Biologia, Universidade Estadual do Sudoeste da Bahia, Jequié, BA, Brasil.
Abstract:
The filamentous fungus Moniliophthora perniciosa is a basidiomycota that causes the witches' broom disease in cocoa trees (Theobroma cacao L.). The mitochondrial DNA polymerase of M. perniciosa (MpmitDNApol) is classified within the B family of DNA polymerases, which can be found in viruses and cellular organelles. Using virtual screening processes, accessing KEGG, PubChem, and ZINC databases, we selected the 27 best putative nucleoside viral-like polymerase inhibitors to test against MpmitDNApol. We used Autodock Vina to perform docking simulations of the selected molecules and to return energy values in several ligand conformations. Then, we used Pymol v1.7.4.4 to check the stereochemistry of chiral carbons, hydrogen bonding receptors, absence or presence of hydrogen, sub and superstructure, numbers of rings, rotatable bonds, and donor groups. We selected the Entecavir Hydrate, a drug used to control hepatitis B; subsequently AMBER 14 was used to describe the behavior of polymerase-entecavir complex after setting up 3500 ps of simulation in water at a temperature of 300 K. From the simulation, a graph of Potential Energy was generated revealing that the ligand remains in the catalytic site after 3500 ps with a final energy of -612,587.4214 kcal/mol.
Insights
Researchers identified Entecavir Hydrate as a potential inhibitor for Moniliophthora perniciosa mitochondrial DNA polymerase (MpmitDNApol). This finding offers a new avenue for developing treatments against the fungus causing witches
Area of Science:
- Molecular Biology
- Mycology
- Drug Discovery
Background:
- Witches' broom disease, caused by Moniliophthora perniciosa, devastates cocoa crops.
- The mitochondrial DNA polymerase (MpmitDNApol) of M. perniciosa is a potential drug target.
- MpmitDNApol belongs to the B family of DNA polymerases, similar to viral and organelle enzymes.
Purpose of the Study:
- To identify potential inhibitors of the Moniliophthora perniciosa mitochondrial DNA polymerase (MpmitDNApol).
- To explore novel therapeutic strategies against witches' broom disease in cocoa trees.
Main Methods:
- Virtual screening of KEGG, PubChem, and ZINC databases identified 27 putative inhibitors.
- Molecular docking simulations using Autodock Vina assessed ligand-polymerase interactions.
- Molecular dynamics simulations with AMBER 14 evaluated the stability of the polymerase-ligand complex.
Main Results:
- Entecavir Hydrate demonstrated stable binding within the MpmitDNApol catalytic site after 3500 ps of simulation.
- The simulation revealed a final potential energy of -612,587.4214 kcal/mol for the polymerase-entecavir complex.
- Stereochemistry and hydrogen bonding interactions were analyzed using Pymol.
Conclusions:
- Entecavir Hydrate shows promise as an inhibitor of MpmitDNApol.
- This study provides a computational basis for developing new treatments targeting M. perniciosa.
- Further experimental validation is warranted to confirm Entecavir Hydrate's efficacy.
