Rahman Md Anisur, Alves Guilherme Bastos, Rolim Silva Gabriel Vinícius, Al-Mutairi Aamal A, Akter Shahina, Yihune Endalamaw, Zaki Magdi E A, Oliveira Jonas Ivan Nobre
Department of pharmacy, Islamic University, Kushtia, 7003, Bangladesh.
Department of Biophysics and Pharmacology, Bioscience Center, Federal University of Rio Grande do Norte, Natal, 59078-970, RN, Brazil.
Sci Rep. 2025 Jul 24;15(1):26922. doi: 10.1038/s41598-025-09835-w.
This study investigates the therapeutic potential of five natural compounds from Carica papaya - olean-12-ene, quercetin, apigenin, luteolin and kaempferol - against dengue virus (DENV) using a multi-faceted in silico approach. Quantum chemical analysis using density functional theory (DFT) revealed insights into the electronic properties and stability, with olean-12-ene exhibiting the highest stability (HOMO-LUMO gap: 6.91 eV), while luteolin and apigenin showed balanced reactivity profiles suitable for biochemical interactions. ADMET profiling underlined the drug-likeness of these compounds: Quercetin showed good solubility (logS: -2.93) and hydrogen bonding potential, apigenin showed high oral bioavailability (HIA: 93.25%) and olean-12-ene exhibited remarkable permeability (Caco-2: 1.26). Molecular docking simulations against the DENV NS2B-NS3 protease, the NS1 protein and the envelope protein provided further insight into their binding affinities and interaction modes. Toxicity assessments indicated manageable risks, although flavonoids exhibited moderate hepatotoxicity and olean-12-ene showed cardiotoxic/nephrotoxic tendencies, suggesting a need for further optimization. Overall, these results highlight the potential of specific papaya-derived compounds, particularly the flavonoids, as candidates for further experimental validation in the development of anti-DENV therapeutics. This work lays a foundation for future in vitro and in vivo studies to combat DENV infection and associated complications such as thrombocytopenia.
本研究采用多方面的计算机模拟方法，研究了番木瓜中的五种天然化合物——齐墩果-12-烯、槲皮素、芹菜素、木犀草素和山奈酚——对登革病毒（DENV）的治疗潜力。使用密度泛函理论（DFT）进行的量子化学分析揭示了电子性质和稳定性的相关见解，其中齐墩果-12-烯表现出最高的稳定性（最高占据分子轨道-最低未占据分子轨道能隙：6.91电子伏特），而木犀草素和芹菜素显示出适合生化相互作用的平衡反应性特征。药物代谢动力学（ADMET）分析强调了这些化合物的类药性质：槲皮素具有良好的溶解性（logS：-2.93）和氢键潜力，芹菜素具有较高的口服生物利用度（人肠道吸收：93.25%），齐墩果-12-烯具有显著的通透性（人结肠腺癌上皮细胞系Caco-2：1.26）。针对登革病毒NS2B-NS3蛋白酶、NS1蛋白和包膜蛋白的分子对接模拟进一步深入了解了它们的结合亲和力和相互作用模式。毒性评估表明风险可控，尽管黄酮类化合物表现出中度肝毒性，齐墩果-12-烯显示出心脏毒性/肾毒性倾向，这表明需要进一步优化。总体而言，这些结果突出了特定番木瓜衍生化合物，特别是黄酮类化合物，作为抗登革病毒治疗药物开发中进一步实验验证候选物的潜力。这项工作为未来对抗登革病毒感染及相关并发症（如血小板减少症）的体外和体内研究奠定了基础。
