Molecular Docking and Dynamics Simulations of Natural Limonoids Interacting with the Nipah Virus Attachment Glycoprotein

INTRODUCTION: The Nipah virus (NiV) belongs to the Paramyxoviridae family and is a zoonotic pathogen associated with severe respiratory disease and encephalitis. Fatality rates of up to 70% of diagnosed cases justify its classification as a biosafety level-4 agent. The absence of specific antiviral therapies underscores the urgent need to identify novel molecular inhibitors. METHODS: This study involved the virtual screening of natural limonoids using molecular docking against the NiV glycoprotein, which is a key target in the adhesion of the virus to human host cells. Subsequently, molecular dynamics simulations were conducted to evaluate the stability of the protein- ligand complexes. RESULTS: Molecular docking results showed that desacetylspathelin (DSP) and nimolicinol (NCL) had the most favourable binding free energy (ΔG) values and relevant interactions with residue Leu124. Molecular dynamics simulations revealed greater structural stability for the DSP-containing complex. DISCUSSION: The observed interaction profiles suggest that these limonoids, particularly DSP, may interact with the NiV glycoprotein, suggesting a possible influence on virus-host adhesion mechanisms. CONCLUSION: These findings suggest that natural limonoids, particularly DSP, are promising candidates for further investigation as potential Nipah virus glycoprotein modulators/inhibitors and could contribute to the development of antiviral strategies.