Exploring the Antiviral Efficacy of Thiophene Derivatives Targeting Human Papillomavirus (HPV) and Prevention of Cancer: A Comprehensive Computational Approach

Abstract

Abstract Human papillomavirus (HPV) infection is a significant public health concern due to its potential to progress into cancer. This diverse group of viruses comprises over 200 distinct types, with some posing minimal health risks, while others have been linked to a range of cancers and genital warts. However, it is very imperative to mitigate this global concern, hence in this study we investigated the antiviral effects of four thiophene derivatives (2B, 2 C, 2D, and 2E) against HPV using a combination of computational approaches, including density functional theory (DFT), molecular docking, and pharmacotoxicity prediction. Our results showed that these compounds exhibit excellent stability, reactivity, and binding affinity with E2 proteins obtained from oncogenic and nononcogenic human papillomaviruses (1R8H), and the LxxLL motifs in HPV E6 oncoproteins (4GIZ). The compounds; 2B, 2 C, 2D, and 2E were docked with 1R8H and 4GIZ. Notably, compound 2E displayed a high binding affinity of -6.4 kcal/mol with the 4GIZ protein. Our findings suggest that these thiophene derivatives have promising antiviral potential against HPV and could be considered as candidates for the development of novel HPV infection therapies. This research also implies that the studied compounds possess the potential to be considered novel antiviral agents, especially against human papillomavirus.