Possible drugs for Huntington’s disease from Capsicum annuum developed using molecular docking against Huntington protein
Abstract
Objective: To evaluate the efficacy of Capsicum annuum as a suitable plant for the treatment of Huntington’s disease using Pyrx. Huntington’s disease results in the damage of the nervous system over a period of time. For this study, we take into consideration Capsaicin, a compound obtained from the fruit of Capsicum annuum (bell pepper) responsible for giving the fruit it’s pungent odor. Studies show that Capsaicin plays a crucial role in the treatment of neurodegenerative diseases like Huntington’s disease by preventing neuronal death. Due to these neuroprotective effects of Capsaicin, this study proposes that other compounds obtained from Capsicum annuum could also display neuroprotective effects and can be evaluated on their ability to treat Huntingtons disease by docking with the mutant Huntington protein.
Methods: Indian Medicinal Plants, Phytochemistry and Therapeutics database was utilized for screening compounds of Capsicum annuum. The mutant Huntington protein was obtained from the National Center of Biological Information and modeled using Swiss model. The selected phytocompounds were screened on Swiss ADME for their Absorption, Digestion, Metabolism and Excretion properties. Pyrx and BIOVIA were then used for molecular docking which simulates the binding of the ligands to the target protein and producing a binding affinity score. Ligands with a higher binding affinity can bind more strongly to the protein and inhibit it’s effect making them suitable treatments.
Results: Certain compounds of Capsicum annuum could bind effectively with the mutant Huntington protein such as Pentyl butyrate and Isobutyl 2-methylbutyrate whereas other compounds that were screened for docking properties did not bind well with the target protein and are not selected for further screening.
Conclusion: Pentyl butyrate can be screened for it’s ability to treat the disease in vivo. Animal testing and clinical trials will prove it’s capability to effectively treat the disease in humans without causing any harmful side effects.
Keywords
References
Tabrizi SJ, Estevez-Fraga C, van Roon-Mom WMC, Flower MD, Scahill RI, Wild EJ, et al. Potential disease-modifying therapies for Huntington’s disease: lessons learned and future opportunities. Lancet Neurol . 2022 ;21(7):645–58. Available from: https://pubmed.ncbi.nlm.nih.gov/35716694/
Snowden JS. The neuropsychology of Huntington’s disease. Arch Clin Neuropsychol [Internet]. 2017 ;32(7):876–87. Available from: https://pubmed.ncbi.nlm.nih.gov/28961886/
Tomczyk M, Glaser T, Ulrich H, Slominska EM, Smolenski RT. Huntingtin protein maintains balanced energetics in mouse cardiomyocytes. Nucleosides Nucleotides Nucleic Acids. 2022;41(3):231–8. Available from: https://pubmed.ncbi.nlm.nih.gov/32933349/
Cortes CJ, La Spada AR. The many faces of autophagy dysfunction in Huntington’s disease: from mechanism to therapy. Drug Discov Today. 2014;19(7):963–71. Available from: http://dx.doi.org/10.1016/j.drudis.2014.02.014
Small changes in protein chemistry play large role in Huntington’s disease. National Institutes of Health (NIH). 2015 [cited 2023 Oct 24]. Available from: https://www.nih.gov/news-events/news-releases/small-changes-protein-chemistry-play-large-role-huntingtons-disease-0
Maisonneuve E, Ezraty B, Dukan S. Protein aggregates: An aging factor involved in cell death. J Bacteriol. 2008;190(18):6070–5. Available from: http://dx.doi.org/10.1128/jb.00736-08
Mandal SK, Rath SK, Logesh R, Mishra SK, Devkota HP, Das N. Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues. Phytother Res . 2023;37(3):965–1002. Available from: https://pubmed.ncbi.nlm.nih.gov/36255140/
McGrady NR, Risner ML, Vest V, Calkins DJ. TRPV1 tunes optic nerve axon excitability in glaucoma. Front Physiol. 2020;11. Available from: https://pubmed.ncbi.nlm.nih.gov/32273850/
Abdel-Salam OME, Mózsik G. Capsaicin, the vanilloid receptor TRPV1 agonist in neuroprotection: Mechanisms involved and significance. Neurochem Res . 2023;48(11):3296–315. Available from: https://pubmed.ncbi.nlm.nih.gov/37493882/
Lastres-Becker I, De Miguel R, De Petrocellis L, Makriyannis A, Di Marzo V, Fernández-Ruiz J. Compounds acting at the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington’s disease. J Neurochem . 2003;84(5):1097–109. Available from: https://pubmed.ncbi.nlm.nih.gov/12603833/
Yang E-J, Song K-S. The ameliorative effects of capsidiol isolated from elicited Capsicum annuum on mouse splenocyte immune responses and neuroinflammation. Phytother Res. 2021 ;35(3):1597–608. Available from: https://pubmed.ncbi.nlm.nih.gov/33124100
National center for biotechnology information. Nih.gov. Available from: https://www.ncbi.nlm.nih.gov/
Swiss-model. Expasy.org.. Available from: https://swissmodel.expasy.org/
Venclovas Č. Methods for sequence–structure alignment. In: Methods in Molecular Biology. Totowa, NJ: Humana Press; 2011. p. 55–82.
Hollingsworth SA, Karplus PA. A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. Biomol Concepts . 2010;1(3–4):271–83. Available from: http://dx.doi.org/10.1515/bmc.2010.022
() AS. IMPPAT. Res.in. . Available from: https://cb.imsc.res.in/imppat/therapeutics/Capsicum%20annuum
PubChem. PubChem. Nih.gov.. Available from: https://pubchem.ncbi.nlm.nih.gov/
SwissADME. Swissadme.ch.. Available from: http://www.swissadme.ch/
Chen X, Li H, Tian L, Li Q, Luo J, Zhang Y. Analysis of the physicochemical properties of acaricides based on lipinski’s rule of five. J Comput Biol . 2020;27(9):1397–406. Available from: https://pubmed.ncbi.nlm.nih.gov/32031890/
ADMETlab 2.0. Scbdd.com. Available from: https://admetmesh.scbdd.com/
Welcome to the PyRx website. Sourceforge.io. Available from: https://pyrx.sourceforge.io/
Systèmes D. Free download: BIOVIA Discovery Studio Visualizer. Dassault Systèmes. 2020. Available from: https://discover.3ds.com/discovery-studio-visualizer-download
Minakawa EN, Nagai Y. Protein aggregation inhibitors as disease-modifying therapies for polyglutamine diseases. Front Neurosci. 2021;15. Available from: http://dx.doi.org/10.3389/fnins.2021.621996
Parzych KR, Klionsky DJ. An overview of autophagy: Morphology, mechanism, and regulation. Antioxid Redox Signal. 2014 ;20(3):460–73. Available from: https://pubmed.ncbi.nlm.nih.gov/23725295/
Researchgate.net. [cited 2023 Oct 25]. Available from: https://www.researchgate.net/profile/Ankit-Sharma-124
DOI: https://doi.org/10.37628/ijaba.v9i2.874
Refbacks
- There are currently no refbacks.