Computational identification of Glycyrrhiza glabra-derived Semilicoisoflavone B and Licoisoflavone B as dual-target inhibitors of Ebola virus proteins

Ebola virus disease (EVD) is a life-threatening zoonotic infection caused by the Ebola virus (EBOV), characterized by high mortality rates and persistent global health concern, with no FDA-approved small-molecule therapeutics currently available. This study investigated Glycyrrhiza glabra phytochemicals as promising dual-target inhibitors of two essential EBOV proteins: matrix protein VP40 and nucleoprotein (NP). An integrated in-silico approach comprising molecular docking, ADMET profiling, 100 ns molecular dynamics simulations, principal component analysis, and density functional theory calculations was employed. Virtual screening of 408 phytocompounds identified two G. glabra -derived phytocompounds, Semilicoisoflavone B and Licoisoflavone B, as promising candidates, exhibiting superior binding affinities (VP40: −10.6 to −9.7 kcal/mol; NP: −9.2 to −8.8 kcal/mol) compared to control ligands Laurifolin and Licochalcone A. Both phytocompounds were identified as promising inhibitors, exhibiting strong binding affinity for both target proteins and favorable pharmacokinetics. Molecular dynamics simulations confirmed stable protein-ligand interactions, with Semilicoisoflavone B showing exceptional affinity for VP40 (ΔG = −129.21 kcal/mol). PCA revealed constrained conformational dynamics, while density functional theory analysis demonstrated favorable electronic properties including narrow HOMO-LUMO gaps (3.69–4.21 eV). These findings suggest Semilicoisoflavone B and Licoisoflavone B as promising dual-target inhibitors of the VP40 and NP of the EBOV; however, further in-vitro and in-vivo studies are necessary to evaluate their therapeutic efficacy.