Computational identification of Ginkgo biloba phytochemicals as dual inhibitors of herpes simplex virus type 1 glycoproteins gB and gD targeting its entry and Alzheimer's disease pathogenesis.

Herpes simplex virus type 1 (HSV-1) causes severe neurological complications such as herpes simplex encephalitis and Alzheimer's disease (AD). Its entry is mediated by glycoproteins gD and gB, which regulate receptor binding and membrane fusion. Targeting these entry glycoproteins represents a promising therapeutic strategy to limit HSV-1 infection and its contribution to AD pathogenesis. Therefore, this study aimed to identify natural dual inhibitors of HSV-1 glycoproteins gB and gD from Ginkgo biloba using an integrated computational approach involving molecular docking, pharmacokinetic, toxicity, and bioactivity profiling, molecular dynamics simulations, and MM-GBSA binding free energy analyses to evaluate binding stability and therapeutic potential. A total of 39 phytochemicals were retrieved from IMPPAT 2.0 and PubChem databases and docked against HSV-1 glycoproteins gB and gD. Pharmacokinetics and toxicity were assessed using admetSAR 3.0, SwissADME, Deep-PK, and pKCSM. Molecular docking revealed several phytochemicals with strong binding affinities to HSV-1 glycoproteins gB and gD, compared to docosanol. Among these, β-sitosterol and ginkgolide A exhibited favorable drug-likeness, acceptable oral bioavailability, no mutagenic and hepatotoxic effects, and biologically active. Molecular dynamic simulation confirmed their greatest binding stability compared to docosanol. MM-GBSA binding free energy analysis further validated their strong and stable interactions within the active sites of HSV-1 glycoproteins gB and gD. These findings identify β-sitosterol and ginkgolide A as promising dual-target inhibitors of HSV-1 glycoproteins gB and gD in context of HSV-1-associated AD pathogenesis. However, experimental validation is required to confirm their antiviral efficacy and potential relevance to AD.