In vitro and in silico antiviral activity of Polyscias scutellaria leaf extract against drug-susceptible and drug-resistant herpes simplex virus and human papillomavirus-positive cervical cancer: implications for topical formulation development.

Herpes simplex virus (HSV) and human papillomavirus (HPV) infections remain major global health concerns, particularly in immunocompromised individuals. Herbal extracts have emerged as promising candidates for developing novel antiviral agents, particularly against drug-resistant viruses. This study examined the inhibitory effects of Polyscias scutellaria (Burm.f.) Fosberg, a tropical ornamental plant with edible young shoots and leaves against HSV, HPV, and cervical cancer cell growth. Four extracts prepared from fresh and dried leaves using ethanolic and hot-water methods were evaluated for their inhibitory activities against drug-susceptible and drug-resistant HSV and HPV, as well as for their effects on CaSki and HeLa cell growth, using plaque inhibition, HPV-16 pseudovirus binding, wound-healing, acridine/ethidium dual staining, and flow cytometry assays. Gene and protein expression levels were analyzed by quantitative qPCR and western blot analysis. The ethanolic extract of fresh P. scutellaria exhibited the strongest inhibitory effects against both wild-type and drug-resistant HSV strains among all extracts tested and downregulated HSV-1 ICP4, UL30, US6 and gC. This extract also suppressed HPV-16 pseudovirus infection at an early stage. In addition, it reduced cancer cell proliferation and increased apoptosis, while suppressing HPV-16/18 E6, BCL2, and NFKB1 expression and upregulating BAX expression. The putatively annotated metabolites with the highest peak area in P. scutellaria, identified using electrospray ionization-quadrupole time-of-flight mass spectrometry, showed favorable drug-likeness and potential interactions with candidate HSV-1 and HPV-16 proteins based on in silico analysis. Notably, a prototype herbal soap containing this extract significantly reduced drug-resistant HSV-1 infection and HPV-16/18 E6 expression. These findings highlight P. scutellaria as a promising natural antiviral and anticancer agent with potential for health-product development.