Andika P. Wardana, First A. Wati, T. Tukiran, Ratih D. Saputri, M. Mitarlis, R. Rinaningsing, Nurina R. Ramadhania, Teguh H. Sucipto, Baso Ilham
Dengue hemorrhagic fever is a mosquito-borne viral disease transmitted by Aedes aegypti and remains a major global health concern due to the lack of specific antiviral therapy. Natural products from medicinal plants represent a promising source of antiviral agents. However, studies focusing on the antiviral potential of Aegle marmelos L. fruit pulp are still limited, particularly using integrated experimental and computational approaches. Therefore, this study aimed to evaluate the anti-dengue activity of the crude methanol extract of A. marmelos fruit pulp and its solvent-partitioned fractions, (i.e. n-hexane and ethyl acetate fractions), and to explore their potential molecular interactions with the dengue virus target protein. The crude extract was obtained by methanol extraction and subsequently fractionated based on polarity, followed by in vitro antiviral and cytotoxicity assays, LC–MS profiling, and molecular docking analysis. The results demonstrated that the crude methanol extract and n-hexane fraction inhibited dengue virus replication with EC₅₀ values of 12.43 and 12.71 µg/mL, respectively, whereas the ethyl acetate fraction showed no detectable activity. The crude extract exhibited the highest selectivity index, indicating a more favorable balance between antiviral efficacy and cytotoxicity. LC–MS analysis revealed diverse phytochemical constituents, and molecular docking of major compounds identified in the active extract showed that the flavonoid derivatives, including rutin and kaempferol glycosides, exhibited favorable binding interactions with the dengue virus protein, supporting their contribution to the observed antiviral activity. These findings provide integrated in vitro and in silico evidence supporting the anti-dengue potential of A. marmelos fruit pulp. © 2026 Wardana et al.
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Surabaya, East Java, Surabaya, Indonesia; Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga, East Java, Surabaya, Indonesia; Department of Chemistry, Universitas Sipatokkong Mambo, South Sulawesi, Indonesia
