MOLECULAR DOCKING OF BIFLAVONOIDS FROM GENUS ARAUCARIA AS DENV NS5 RNA-DEPENDENT RNA POLYMERASE INHIBITOR USING YASARA AND PLANTS PROGRAMS

LAKSMI AMBARSARI; NAJMA AULIA NUR; SYIFA SILFANI RODOTUL ZANAH; KURNIAWANTI; HANHAN DIANHAR; SITI WARNASIH; DYAH UTAMI CAHYANING RAHAYU; PURWANTININGSIH SUGITA

doi:10.22159/ijap.2024v16i5.50833

Authors

LAKSMI AMBARSARI Department of Biochemistry, Faculty Mathematics and Natural Sciences, IPB University, Bogor, Jawa Barat, Indonesia
NAJMA AULIA NUR Department of Biochemistry, Faculty Mathematics and Natural Sciences, IPB University, Bogor, Jawa Barat, Indonesia https://orcid.org/0009-0001-6613-4998
SYIFA SILFANI RODOTUL ZANAH Department of Chemistry, Faculty Mathematics and Natural Sciences, IPB University, Bogor, Jawa Barat, Indonesia
KURNIAWANTI Department of Chemistry, Faculty Mathematics and Natural Sciences, IPB University, Bogor, Jawa Barat, Indonesia https://orcid.org/0000-0002-7612-5964
HANHAN DIANHAR Chemistry Study Program, State University of Jakarta, Jakarta, Indonesia https://orcid.org/0000-0001-8599-3619
SITI WARNASIH Chemistry Study Program, Faculty Mathematics and Natural Sciences, Pakuan University, Bogor, Jawa Barat, Indonesia https://orcid.org/0000-0002-2413-0059
DYAH UTAMI CAHYANING RAHAYU Department of Chemistry, Faculty Mathematics and Natural Sciences, Universitas Indonesia, Depok, Jawa Barat, Indonesia https://orcid.org/0000-0002-0663-7526
PURWANTININGSIH SUGITA Department of Chemistry, Faculty Mathematics and Natural Sciences, IPB University, Bogor, Jawa Barat, Indonesia https://orcid.org/0000-0002-0305-8123

DOI:

https://doi.org/10.22159/ijap.2024v16i5.50833

Keywords:

Genus araucaria, Biflavonoids, In silico with YASARA structure and PLANTS programs, 7,4',7''-tri-O-methylagathisflavone (BF3)

Abstract

Objective: This study aimed to screen 23 biflavonoids (23 BF) from the Araucaria genus to identify the most promising compound for anti-dengue fever antivirus treatment using in silico techniques with yet another scientific artificial reality application (YASARA) Structure and the Protein-Ligand ANT System (PLANTS) programs.

Methods: Predictions of conserved amino acids and potential pockets of the virus dengue NS5 RNA-dependent RNA polymerase (DENV NS5 RdRp) (PDB ID: 5K5M) were examined, while co-crystal ligands were prepared along with 23 biflavonoids. Molecular docking of ligands on the target protein was carried out using the YASARA Structure and PLANTS programs. The interactions were visualized with LigPlot+, Pymol, and Discovery Studio 2021 Client in. pdb format.

Results: The results showed that based on the molecular docking of 23 biflavonoids from the Araucaria genus against the selected DENV NS5 RdRp, the top nine compounds with great potential as antiviral drug candidates were identified. Among these compounds, 7,4’,7’’-tri-O-methylagathisflavone (BF3) was distinct as the best choice based on the analysis conducted using the YASARA Structure and PLANTS programs. Other compounds, including 7,4',4'''-tri-O-methylamentoflavone (BF10), 4',4'''-di-O-methylamentoflavone (BF11), 7,4',7'',4'''-tetra-O-methylamentoflavone (BF12), 7''-O-methylamentoflavone (BF13), and 7,7''-di-O-methylamentoflavone (BF14), were selected through the YASARA Structure program, while 7,4',7'',4'''-tetra-O-methylagathisflavone (BF8) and 7''-O-methylrobustaflavone (BF23) were selected from the PLANTS program. All compounds had lower free energy (∆G), dissociation constant (Kd), and docking scores compared to the reference ligand, balapiravir. Hydrogen and hydrophobic bonds were formed with the protein through conserved amino acid residues, the N-pocket, and the catalytic Gly-Asp-Asp (GDD) site.

Conclusion: The algorithm differences between the YASARA Structure and PLANTS programs led to the selection of the best compound 7,4',7''-tri-O-methylagathisflavone (BF3) as a candidate antiviral drug for dengue hemorrhagic fever.

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