Virtual screening and molecular dynamics studies of antivenom using flavonoid compounds derived from Andrographis...

The antivenom potential of Andrographis echioides (A. echioides), a traditional medicinal herb, was investigated using a comprehensive in silico approach to address the limitations of conventional antivenoms against Russell's viper envenomation. This study aimed to conduct virtual screening and molecular dynamics (MD) studies of flavonoid compounds from A. echioides to explore their potential as antivenom agents. Gas chromatography-mass spectrometry (GC-MS) analysis identified 84 bioactive phytochemicals in the leaf extracts. The selected flavonoid constituents were evaluated for their predicted inhibitory potential against venom-associated enzymes using molecular docking with the iGEMDOCK software. The target proteins included metalloproteinase (PDB ID: 2E3X), serine proteinase (PDB ID: 3S9A), and human pancreatic phospholipase A2 (PDB ID: 6Q42). Among the screened compounds, decanoic acid (- 93.7429 kcal/mol), oxalic acid 6-ethyloct-3-yl isohexyl ester (- 91.6448 kcal/mol), and oxalic acid 6-ethyloct-3-yl hexyl ester (- 85.7934 kcal/mol) exhibited the highest binding affinities to the target protein and compared them with the standard compound. Drug-likeness analysis confirmed the favorable pharmacokinetic properties of compounds. MD simulations spanning 100 ns revealed stable binding interactions, consistent RMSD values, favorable hydrogen bonding patterns, and stable structural dynamics. This is the first study to report the antivenom potential of bioactive compounds from this species using computational methods. These computational insights suggest that flavonoid constituents derived from A. echioides may possess promising binding and predicted inhibitory activities against key venom enzymes, warranting further investigation as potential natural antivenom agents.