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Abstract 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. 1 E 98aminoacid, 98aminoacid aminoacid 98 amino acid, 98-amino-acid 11kilodalton kilodalton 11 portions pRbE2F pRbEF E2F F complex CKII mostly p21, p , p21) HDAC1 HDAC regulation Here compounds thiazolo3,2abenzimidazole32Hone,22fluorobenzylideno7,8dimethyl thiazolo32abenzimidazole32Hone22fluorobenzylideno78dimethyl thiazoloabenzimidazoleHonefluorobenzylidenodimethyl 3,2 benzimidazole 3 2H one,2 2 fluorobenzylideno 7,8 dimethyl one 7 8 H thiazolo, (thiazolo) control analysis site E7mediated Emediated mediated p2 progression immortalization proliferation addition CKIImediated p13 simulation compound protein preferable 9 pRbE EF thiazolo3 2abenzimidazole32Hone 22fluorobenzylideno7 8dimethyl abenzimidazole Hone 32 3, one2 one, 78 7, (thiazolo p1 abenzimidazoleHone 22fluorobenzylideno