In Silico Evaluation of Natural Compounds as Dual Inhibitors of Exotoxin A and LasB (Elastase) Virulence Proteins in Pseudomonas aeruginosa

Andrias Bayu Fariska; Linda Erlina; Ade Arsianti; Aryo Tedjo

doi:10.24036/eksakta/vol26-iss04/631

EKSAKTA: Berkala Ilmiah Bidang MIPA

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In Silico Evaluation of Natural Compounds as Dual Inhibitors of Exotoxin A and LasB (Elastase) Virulence Proteins in Pseudomonas aeruginosa

Andrias Bayu Fariska ¹

, Linda Erlina ²

, Ade Arsianti ²

, Aryo Tedjo ²

¹ Master Programs in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

² Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Published 2025-12-30

Vol. 26 No. 04 (2025) PAGES 480-499

DOI 10.24036/eksakta/vol26-iss04/631

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Abstract

Pseudomonas aeruginosa is an opportunistic pathogen whose virulence is largely mediated by Exotoxin A and LasB (elastase), making them promising anti-virulence drug targets. This study aimed to evaluate the inhibitory potential of natural compounds against these two key proteins using an in silico approach. Pharmacophore-based virtual screening of HerbalDB compounds was performed by LigandScout software, followed by molecular docking using AutoDockTools-1.5.7 against Exotoxin A (PDB ID: 1AER) and LasB (PDB ID: 1U4G). Native ligands and co-crystallized inhibitors were used as docking controls to validate binding accuracy. Among the screened compounds, Epicatechin-(4β-6)-epicatechin-(4β-8)-catechin exhibited the strongest binding affinity to Exotoxin A (ΔG = −10.72 kcal·mol⁻¹), while Carpaine showed the highest affinity for LasB (ΔG = −8.91 kcal·mol⁻¹). The predicted interactions involved hydrogen bonds and hydrophobic interactions with active-site residues, comparable to the native inhibitors. Furthermore, ADMET analysis indicated favorable pharmacokinetic and drug-likeness properties. These findings suggest that selected natural compounds possess potential dual inhibitory activity against Exotoxin A and LasB, warranting further experimental validation as anti-virulence candidates for controlling P. aeruginosa infections.

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In Silico Evaluation of Natural Compounds as Dual Inhibitors of Exotoxin A and LasB (Elastase) Virulence Proteins in Pseudomonas aeruginosa

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