Arief Hidayatullah, Diana Widiastuti, Wira Eka Putra, Muhaimin Rifa’i, Muhammad Fikri Heikal, Sustiprijatno
Infection of keratinocytes by high-risk human papillomavirus (HPV) strains, notably HPV16, is responsible for the onset of cervical cancer. The E6 protein serves as a pivotal oncoprotein implicated in the progression of cancer. We utilised a virtual screening method to identify bioactive compounds in a variety of commonly used medicinal plants in Indonesia. All the top five compounds bind to a single binding site on the E6 major hydrophobic groove, which corresponds to the binding site for the E6AP and IRF3’s LxxLL motifs. They are expected to function as competitive inhibitors, inhibiting the development of the E6-E6AP and E6-IRF3 complexes, which limit p53 degradation and therefore cell proliferation, thus preserving the innate immune response to HPV16 infection. Asarinin and thiazolo[3,2-a]benzimidazole-3(2H)-one,2-(2-fluorobenzylideno)-7,8-dimethyl were predicted to be the most effective compounds in this research owing to their strong affinity for and persistent interactions with the E6 major hydrophobic groove, particularly in comparison to pharmacological controls. © Penerbit Universiti Sains Malaysia, 2025.
Democratic Governance and Poverty Reduction Unit, United Nations Development Programme, Eijkman-RSCM Building, Jl. Diponegoro 69, Jakarta, 10430, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Pakuan, Jl. Pakuan, RT.02/RW.06, Tegallega, West Java, Bogor, 16129, Indonesia; Biotechnology Study Program, Department of Applied Sciences, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, Jl. Semarang 5, East Java, Malang, 65145, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, East Java, Malang, 65145, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Malang, Jl. Semarang 5, East Java, Malang, 65145, Indonesia; Research Center for Applied Botany, National Research and Innovation Agency, Jl. Raya Jakarta-Bogor Km 46, West Java, Cibinong-Bogor, 16911, Indonesia
