PreprintArticleVersion 1This version is not peer-reviewed
Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy
Version 1
: Received: 3 September 2024 / Approved: 3 September 2024 / Online: 5 September 2024 (06:59:08 CEST)
How to cite:
Lukman, Y.; Yusuf, A. Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy. Preprints2024, 2024090270. https://doi.org/10.20944/preprints202409.0270.v1
Lukman, Y.; Yusuf, A. Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy. Preprints 2024, 2024090270. https://doi.org/10.20944/preprints202409.0270.v1
Lukman, Y.; Yusuf, A. Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy. Preprints2024, 2024090270. https://doi.org/10.20944/preprints202409.0270.v1
APA Style
Lukman, Y., & Yusuf, A. (2024). Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy. Preprints. https://doi.org/10.20944/preprints202409.0270.v1
Chicago/Turabian Style
Lukman, Y. and Abdulhaqeem Yusuf. 2024 "Computational and Pharmacological Evaluation of Capsaicin-Mediated Inhibition of HPV 16 E6 and E7 Oncoproteins: Molecular Mechanisms and Implications for Cervical Cancer Therapy" Preprints. https://doi.org/10.20944/preprints202409.0270.v1
Abstract
Cervical cancer remains a significant global health challenge, ranking as the fourth most common cancer among women. The primary causative agents, Human papillomavirus (HPV) strains 16 and 18, are well-known for their role in cervical carcinogenesis, primarily through the actions of the E6 and E7 oncoproteins. This study aimed to identify a natural compound capable of inhibiting both E6 and E7 oncoprotein activities, thereby offering a potential therapeutic approach using a single agent.
This study also comprises an extensive in silico analysis with molecular docking studies by AutoDock Vina and Schrodinger Maestro to analyse the binding affinity, hydrogen bonds interactions of selected compounds against HPV 16 E6 &E7 proteins. GROMACS package and iMODS server was used to perform molecular dynamics simulations of protein-ligand complexes to elucidate stability of the ligands around the receptor at different time points. SwissADME was utilized for the prediction of pharmacokinetic properties while PROTOX-II helped in predicting toxicological data
Capsaicin emerged as the most promising candidate, exhibiting binding energies of -7.3 kcal/mol and -5.6 kcal/mol against the HPV 16 E6 and E7 proteins, respectively. Notably, Capsaicin formed a single hydrogen bond with each oncoprotein, indicating a strong and specific interaction. The compound also demonstrated a favourable pharmacokinetic profile, with no violations of drug-likeness rules, and was classified as Toxicity Class 4, suggesting a moderate safety profile.
These results, thus branding Capsaicin as a promising lead compound for further investigations in cervical cancer therapy that deserves documentation through well-equipped wet lab experiments followed by clinical studies.
Keywords
Human papillomavirus; HPV 16 oncoproteins; Capsaicin; E6 and E7 oncoproteins; Molecular docking; ADMET studies; Molecular dynamic simulations
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
