Arief Hidayatullah, Wira E. Putra, Sustiprijatno, Muhaimin Rifa’i, Diana Widiastuti, Muhammad F. Heikal, Galuh W. Permatasari
The Human papillomaviruses type 16 E7 oncoprotein is a 98-amino-acid, 11-kilodalton acidic oncoprotein with three conserved portions. Due to its interaction with the pRb-E2F complex, CKII, CKI (mostly p21), and even HDAC1, it possesses strong transformative and carcinogenic qualities that inhibit normal differentiation and cell cycle regulation. Here, we target the E7 oncoprotein using two prior research active compounds: asarinin and thiazolo[3,2-a]benzimidazole-3(2H)-one,2-(2-fluorobenzylideno)-7,8-dimethyl (thiazolo), and valproic acid as a control. We are performing molecular docking followed by molecular dynamic analysis. By acting as competitive inhibitors in the binding site, it was hypothesized that both drugs would inhibit E7-mediated pRb degradation and E7-mediated p21 degradation, resulting in decreased cell cycle progression, immortalization, and proliferation. In addition, we expect that the direct inhibitory action of valproic acid in E7 will target the CKII-mediated phosphorylation pathway necessary for destabilizing p130 and pRb. According to the results of the dynamic simulation, stable interactions exist between every compound. Despite the instability of E7 protein, stability results indicate that both natural chemicals are preferable, with thiazolo outperforming valproic acid. © 2023, Academia Brasileira de Ciencias. All rights reserved.
United Nations Development Programme Indonesia, Health Governance Initiative, Eijkman-RSCM Building, Jakarta, 10430, Indonesia; Universitas Negeri Malang, Biotechnology Study Program, Department of Applied Sciences, Faculty of Mathematics and Natural Sciences, East Java, 65145, Indonesia; National Research and Innovation Agency, Research Center for Plant Conservation, Botanic Gardens and Forestry, Cibinong, West Java, Bogor, 45262, Indonesia; Brawijaya University, Department of Biology, Faculty of Mathematics and Natural Sciences, East Java, 65145, Indonesia; Universitas Pakuan, Department of Chemistry, Faculty of Mathematics and Natural Science, West Java, 45262, Indonesia; Khon Kaen University, Tropical Medicine International Program, Faculty of Medicine, Khon Kaen, 40000, Thailand; Indonesian Research Institute for Biotechnology and Bioindustry, West Java, Bogor, 45262, Indonesia