Fruit-derived bioactive compounds of Malus domestica as novel therapeutic inhibitors against Monkeypox and Marburg virus: A computational based drug discovery study

Abstract

Malus domestica, commonly known as apple, possesses several pharmacological activities. However, its potential antiviral effects have not been explored. This study investigates bioactive compounds derived from Malus domestica as potential therapeutic agents against Monkeypox and Marburg viruses using computer-aided drug discovery techniques. Activity spectrum prediction (Prediction of Activity Spectra for Substances, PASS) identified key phytochemicals ursolic acid (UA), rutin (RTN), and isoquercitin (IQCN) as exhibiting high probabilities of antiviral activity, though slightly lower than the standard antiviral agent cidofovir (CDV). Molecular docking studies confirmed stable interactions between the selected compounds and viral target proteins, 4QWO, a protein structure associated with monkeypox virus, and 4OR8, related to the Marburg virus. Results demonstrated that procyanidin B2 (PCB2), ursolic acid (UA), and vitamin D3 (VTD3) exhibited strong binding affinities of –7.7, –7.7, and –7.3 kcal/mol, respectively, with the 4QWO, surpassing CDV (–4.3 kcal/mol). Similarly, chlorogenic acid (CA), quercitrin (QCN), and RTN showed binding affinities of –7.9, –7.9, and –8.4 kcal/mol, respectively, with the 4OR8, compared to CDV (–6.0 kcal/mol). Ligand-receptor interaction analysis revealed multiple hydrogen bonds and conserved residue contacts, supporting high specificity and stability. Pharmacokinetic and toxicity profiles, predicted using absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, indicated favorable properties and lower toxicity for CA, UA, and RTN relative to CDV. These findings highlight the potential of Malus domestica-derived phytochemicals as promising antiviral candidates. Nonetheless, further validation through in vitro and in vivo studies is essential to substantiate their therapeutic utility against Monkeypox and Marburg viruses.