Exploration of the antiviral efficacy of thiophene derivatives targeting human papillomavirus (HPV) and prevention of cancer: A comprehensive computational approach

Abstract

Abstract Owing to the public health concern of human papillomavirus infection, which is capable of progressing into cancer among the population today, desperation to mitigate the cause of this infection is needed; hence, in this research, we unveiled the antiviral effects of four thiophene derivatives, 2B, 2C, 2D and 2E, against human papillomavirus (HPV) via computational DFT and molecular docking approaches along with ADMET prediction. Interestingly, the compounds showed great stability according to conformational assessment, spectroscopic studies (FT-IR and UV‒Vis), NBO studies, and quantum descriptor analysis. These compounds mostly exhibit LP→ LP, σ*→ σ*, and σ*→ σ transitions, as 2B shows a dominant π*→ π* orbital transition. Their reactivity was observed in different studies; for example, the HOMO-LUMO and DOS results highlighted 2B as the most reactive, among others. The energy gaps were 3.758 eV, 3.750 eV, 3.743 eV, and 3.724 eV for 2B, 2C, 2D, and 2E, respectively. During the docking process, the compounds displayed a high binding affinity and number of amino acids after interacting with the 1R8H and 4GIZ proteins of HPV, especially when they interacted with the 4GIZ protein, as the 2E-4GIZ complex displayed a robust affinity of -6.4 kcal/mol. Hence, these compounds show great antiviral potential against HPV and are promising candidates for novel HPV infection therapies.