Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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In silico discovery and evaluation of phytochemicals binding mechanism against human catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in Parkinson disease

  • Rath, Surya Narayan (Department of Bioinformatics, Odisha University of Agriculture and Technology) ;
  • Jena, Lingaraja (Centers for Advanced Research & Excellence, Department of Laboratory Oncology, All India Institute of Medical Science) ;
  • Bhuyan, Rajabrata (Department of Bio-Science and Biotechnology, Banasthali Vidyapeeth (Deemed) University) ;
  • Mahanandia, Nimai Charan (Animal Biotechnology Centre, National Dairy Research Institute) ;
  • Patri, Manorama (Neurobiology Laboratory, Department of Zoology, School of Life Sciences, Ravenshaw University)
  • Received : 2020.10.20
  • Accepted : 2020.11.05
  • Published : 2021.03.31
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Abstract

Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.

Keywords

Acknowledgement

We are thankful to all members of Neurobiology laboratory, Department of Zoology, Ravenshaw University, Cuttack, and Department of Bioinformatics, Odisha University of Agriculture and Technology, Bhubaneswar for technical support and valuable discussions.

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