Cervical cancer remains a significant global health concern that starts in the cervix, the lower part of the uterus that connects to the vagina and is caused by the human papillomavirus (HPV), necessitating the development of effective multitargeted effective and resistance-proof
therapies. In early-stage
cervical cancer may not show any symptoms, however, as the
cancer progresses, some people may experience- abnormal
vaginal bleeding, watery or bloody
vaginal discharge,
pain in the pelvis or
lower back, pain during sex, and frequent and painful urination. In this study, we screened the complete FDA-approved
drug library using a multitargeted inhibitory approach against four
cervical cancer proteins, namely mitotic arrest deficient -2,
DNA polymerase epsilon B-subunit,
benzimidazole-related -1, and
threonine-
protein kinase-1 which crucially plays its role for the in its development process. We employed the HTVS, SP and XP algorithms for efficient filtering and screening that helped to identify
Mitoxantrone 2HCl against all of them with docking and MM\GBSA scores ranging from - 11.63 to - 7.802 kcal/mol and - 74.38 to - 47.73 kcal/mol, respectively. We also evaluated the interaction patterns of each complex and the pharmacokinetics properties that helped gain insight into interactions. Subsequently, we performed multiscale MD simulations for 100 ns to understand the dynamic behaviour and stability of the
Mitoxantrone 2HCl -
protein complexes that revealed the formation of stable
drug-
protein complexes and provided insights into the molecular interactions that contribute to
Mitoxantrone's inhibitory effects on these
proteins and can be a better
drug for
cervical cancer. However, experimental studies of these findings could pave the way for
therapies to combat
cervical cancer effectively.