In-silico investigations of bioactive compounds from ginger against Lassa fever virus nucleoprotein

The Lassa fever virus (LFV) has a nucleoprotein (NP) complexed with deoxythymidine triphosphate (dTTP) that suppresses interferon activity, while also being involved in RNA synthesis, making it an excellent target for anti-LFV therapeutics and vaccines. In this study, we evaluated the anti-LFV potential of four bioactive compounds, shogaol, 6-gingerol, 8-gingerol, and 10-gingerol, in silico against 3MX2. Using standard protocols, we performed molecular docking between these ligands against the active site of the LFV NP, a 300 ns molecular dynamics simulation run, dynamic cross-correlation, principal component analysis (PCA) and eigenvalue rank plots, density functional theory (DFT), and prediction of pharmacokinetics properties. The ligands produced favourable docking affinities that ranged from - 7.4 to - 7.7 kcal/mol. The docking poses revealed the interacting amino acid residues within the active site of the NP 3MX2, implicated in viral RNA synthesis and replication. The poses and ligand interaction analyses revealed the formation of water bridges, hydrogen, ionic and pi-pi stacks bonds. Molecular dynamics simulation revealed the formation of stable complexes, especially for 8-gingerol. The PCA and cross-correlational analyses revealed conformational changes in the complexes and net positive interacting amino acid residues. DFT analysis revealed small energy gaps indicative of reactivity. The ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity), SASA (Solvent Accessible Surface Area), PSA (Polar Surface Area), and MolSA (Molecular Surface Area) evaluations indicate that the ligands are good oral drug candidates. The favourable in silico findings support the anti-LFV potentials of the ligands and warrants further in vivo evaluations.