In Silico Docking to Explicate Interface between Plant-Originated Inhibitors and E6 Oncogenic Protein of Highly

Satish Kumar1, Lingaraja Jena1, Maheswata Sahoo1

  • 1Bioinformatics Centre & Biochemistry, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442-102, India.

Insights

Natural compounds show promise in fighting human papillomavirus (HPV) by inhibiting the E6 oncoprotein. This study used structure-based drug design to identify compounds that could restore tumor suppressor p53 protein function.

Area of Science:

  • Oncology
  • Virology
  • Drug Discovery

Background:

  • Human papillomavirus (HPV) infection is a leading cause of cancer mortality in women worldwide.
  • The E6 oncoprotein of high-risk HPV strains, like HPV18, inactivates the tumor suppressor p53 protein, promoting cancer development.
  • Natural compounds have historically been explored for their therapeutic potential in cancer treatment.

Purpose of the Study:

  • To investigate the potential of various natural compounds as inhibitors of the HPV18 E6 oncoprotein.
  • To elucidate the molecular mechanisms by which these natural compounds interact with the E6 oncoprotein.
  • To identify natural compounds capable of restoring the function of the tumor suppressor p53 protein.

Main Methods:

  • Structure-based drug designing approach was employed.
  • Molecular docking analysis was performed to predict interactions between natural inhibitors and the HPV18 E6 oncoprotein.
  • In silico validation of natural compounds was conducted.

Main Results:

  • Docking analysis revealed interactions between several natural inhibitors and the p53 binding site (residues 108-117, CQKPLNPAEK) of the HPV18 E6 oncoprotein.
  • These interactions suggest a mechanism for reinstating normal p53 functioning.
  • The study provided in silico validation for the efficacy of these natural compounds against HPV oncoproteins.

Conclusions:

  • Natural compounds can effectively inhibit the HPV18 E6 oncoprotein.
  • The identified natural compounds have the potential to restore p53 tumor suppressor activity.
  • This research offers a foundation for developing novel anti-cancer therapeutics derived from natural sources against HPV infections.

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