In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management

Abstract

Cervical cancer (CC) is the fourth most common pathology in women worldwide and presents a high impact in developing countries due to limited financial resources as well as difficulties in monitoring and access to health services. Human papillomavirus (HPV) is the leading cause of CC, and despite the approval of prophylactic vaccines, there is no effective treatment for patients with pre-existing infections or HPV-induced carcinomas. High-risk (HR) HPV E6 and E7 oncoproteins are considered biomarkers in CC progression. Since the E6 structure was resolved, it has been one of the most studied targets to develop novel and specific therapeutics to treat/manage CC. Therefore, several small molecules (plant-derived or synthetic compounds) have been reported as blockers/inhibitors of E6 oncoprotein action, and computational-aided methods have been of high relevance in their discovery and development. In silico approaches have become a powerful tool for reducing the time and cost of the drug development process. Thus, this review will depict small molecules that are already being explored as HR HPV E6 protein blockers and in silico approaches to the design of novel therapeutics for managing CC. Besides, future perspectives in CC therapy will be briefly discussed.

Repositioning of Anti-Inflammatory Drugs for the Treatment of Cervical Cancer Sub-Types

“…In addition, most of these procedures can damage normal tissues and have potential adverse effects, such as bleeding, which can make patients uncomfortable and affect quality of life. This is another reason to focus on HPV-related carcinogenesis, which can be treated with anti-inflammatory drugs that are cheap, easy to obtain, and associated with tolerable side effects ( Gomes et al, 2021 ).…”

Taxifolin and Lucidin as Potential E6 Protein Inhibitors: p53 Function Re-Establishment and Apoptosis Induction in Cervical Cancer Cells

“…Current treatments consist of surgery, radiotherapy, and chemotherapy, which cause infertility, several side effects to patients, and are expensive [ 7 , 36 ]. Considering that the p53 function is abrogated by the E6 protein in HPV-induced cancers, one line of investigation to pursue is the discovery of anticancer agents that could block the E6 protein’s role [ 17 , 42 ]. According to the literature, the focus has been on the inhibition of the E6/E6AP interaction, and a recently published work explored the direct interaction of E6/p53 proteins [ 12 , 17 ].…”

“…In line with this, computer-aided drug design techniques have been employed to reduce time and costs as well as accelerate drug development [ 15 , 16 ]. For example, methods such as molecular docking and molecular dynamics simulations have been used to select promising molecules from large libraries by predicting the orientation of a compound to the target, their interactions, and binding stability [ 17 ].…”

Natural Bioactives: Back to the Future in the Fight against Human Papillomavirus? A Narrative Review

“…The options available for therapy of HPV cancers (i.e., surgery, and chemo- and radio-therapy) are insufficient. Novel promising targeted agents with potential anti-HPV cancer effects comprise repurposed drugs (i.e., rimantadine) [ 11 ], in silico defined small molecules [ 12 ], and immunotherapeutics such as CAR-T cells, immune checkpoint inhibitors (ICIs), single-chain intrabodies, and therapeutic vaccines [ 13 , 14 , 15 , 16 ].…”