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A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
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.
Abstract:
The leading cause of cancer mortality globally amongst the women is due to human papillomavirus (HPV) infection. There is need to explore anti-cancerous drugs against this life-threatening infection. Traditionally, different natural compounds such as withaferin A, artemisinin, ursolic acid, ferulic acid, (-)-epigallocatechin-3-gallate, berberin, resveratrol, jaceosidin, curcumin, gingerol, indol-3-carbinol, and silymarin have been used as hopeful source of cancer treatment. These natural inhibitors have been shown to block HPV infection by different researchers. In the present study, we explored these natural compounds against E6 oncoprotein of high risk HPV18, which is known to inactivate tumor suppressor p53 protein. E6, a high throughput protein model of HPV18, was predicted to anticipate the interaction mechanism of E6 oncoprotein with these natural inhibitors using structure-based drug designing approach. Docking analysis showed the interaction of these natural inhibitors with p53 binding site of E6 protein residues 108-117 (CQKPLNPAEK) and help reinstatement of normal p53 functioning. Further, docking analysis besides helping in silico validations of natural compounds also helped elucidating the molecular mechanism of inhibition of HPV oncoproteins.
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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