Structure-Guided Discovery of 2-Phenylethanol as a Dual-Target Antifungal and Antiviral Agent: Integrative Docking, Dynamics, and ADMET Profiling Against Key Pathogenic Enzymes

The growing threat of multidrug-resistant fungal and viral pathogens underscores the urgent need for novel broad-spectrum therapeutics. In this study, we computationally evaluated the dual antimicrobial potential of 2-phenylethanol (2 PE), a phenyl-substituted aromatic alcohol derived from Plumeria rubra, against seven biologically essential targets using molecular docking, molecular dynamics (MD) simulations, and ADMET profiling. Docking studies revealed high binding affinities of 2 PE across fungal enzymes—Candida albicans N-myristoyltransferase, Aspergillus niger endoglucanase A, and Penicillium chrysogenum Sec3p–Rho1p—and viral enzymes—SARS-CoV-2 main protease, HIV-1 reverse transcriptase, HIV-1 protease, and hepatitis B virus capsid protein—with docking scores ranging from − 9.1 to − 14.4 kcal/mol. Key interactions included hydrogen bonding with catalytically critical residues such as His41, Cys145, Arg187, and Ser111. MD simulations over 100 ns confirmed structural stability of all complexes, with low RMSD (< 2.3 Å), consistent ligand positioning, stable radius of gyration, and persistent hydrogen bonding (> 80% occupancy). ADMET analysis indicated high intestinal absorption, low toxicity, non-mutagenicity, and minimal environmental risk, reinforcing the bioavailability and safety profile of 2 PE. The compound’s favorable physicochemical properties, natural origin, and target-specific binding support its candidacy as a dual-action antiviral and antifungal agent. Although entirely in silico, these findings provide a mechanistic rationale for further in vitro and in vivo evaluation, including enzymatic inhibition assays, microbial growth studies, and structure–activity optimization. This study establishes 2 PE as a promising lead molecule for next-generation broad-spectrum antimicrobial development.