Phytoestrogens 7-O-acetylformonetin and khrinone A from Pterocarpus soyauxii Taub. inhibit the human papillomavirus replication: An integrative immunological, chemical, and computational approach to cervical cancer prevention

Cervical cancer is mainly caused by persistent infection with high-risk human papillomavirus (HPV), particularly HPV16. Current therapeutic strategies are limited by their toxicity and the persistence of the virus, highlighting the need to find safer alternatives. Pterocarpus soyauxii, widely used in African ethnopharmacology, has yielded new phytoestrogens such as 7-O-acetylformononetin and khrinone A, which may have antiviral and anticancer potential. This study aimed to investigate the potential of 7-O-acetylformononetin and khrinone A to prevent HPV-induced cervical carcinogenesis by targeting viral and host oncogenic proteins using integrative computational approaches. This approach limits the use of animals for experimental testing and provides valuable data on the activity of plant-derived compounds. A network pharmacology approach was applied using STRING and Metascape to identify key molecular targets and pathways. Molecular docking was performed with BC-Dock2 and BIOVIA Discovery Studio to evaluate the binding affinities of phytochemical compounds to HPV-related proteins. Density functional theory (DFT) analyses were conducted to evaluate electronic properties and stability. The central proteins analyzed included HPV16E6, MDM2, CSNK2A2, mTOR, and HDAC1. Network pharmacology revealed strong associations with central pathways of HPV-induced carcinogenesis, notably the PI3K/Akt/mTOR signaling pathway, p53 regulation, and epigenetic remodeling. Docking results demonstrated high-affinity interactions between both compounds and HPV16E6 and MDM2, suggesting a stabilization of p53′s tumor-suppressive activity. Interactions with CSNK2A2 and HDAC1 indicated a potential modulation of kinase signaling and histone deacetylation. DFT analyses confirmed favorable molecular stability and drug-likeness, confirming their pharmacological potential. 7-O-acetylformononetin and khrinone A from Pterocarpus soyauxii exhibit strong potential as multitarget agents capable of interfering with HPV-mediated oncogenic processes. These results link ethnopharmacological knowledge with computational pharmacology, offering new avenues for the development of natural therapeutic agents for cervical cancer.