In Silico Screening of Neem-Derived Phytochemicals Targeting the Avr1 (SIX4) Effector Protein of Fusarium oxysporum for Fusarium Wilt Management

Abstract

Fusarium wilt, caused by Fusarium oxysporum, is a destructive soil-borne disease that severely limits crop productivity worldwide. Its effector protein Avr1 plays a key role in suppressing host immune responses. In this study, an integrated in silico approach was employed to identify potential natural inhibitors of Avr1 using neem (Azadirachta indica) derived phytochemicals. Ten compounds were screened through molecular docking, ADME profiling, and toxicity prediction. Docking results revealed binding affinities ranging from -6.3 to -5.5 kcal/mol, with nimbiol showing the strongest interaction (-6.3 kcal/mol). The highest-ranking protein-ligand complex was stabilized by hydrophobic and electrostatic interactions involving key residues such as ARG180, VAL158, LYS182, and TYR134, indicating a favorable binding environment. ADME analysis demonstrated acceptable pharmacokinetic properties and drug-likeness for several compounds, specially nimbiol and gedunin, with high gastrointestinal absorption and compliance with Lipinskis rule of five. Toxicity prediction indicated moderate hepatotoxicity and low carcinogenic potential, although elevated immunotoxicity was observed across most ligands. Overall, the findings align with existing studies on neems antifungal potential and highlight nimbiol and gedunin as promising lead compounds for further experimental validation against Fusarium wilt.