RESEARCH ARTICLE


Network Biology Approaches to Identify the Drug Lead Molecule for Neurodevelopmental Disorders in Human



Archana Verma1, Shweta Singh Chauhan1, Vaishali Pankaj1, Neha Srivastva1, 2, Prachi Srivastava1, *
1 AMITY Institute of Biotechnology, AMITY University Uttar Pradesh Lucknow Campus, UP, India
2 Dr. A.P.J. Abdul Kalam Technical University, Lucknow, UP, India


© 2020 Verma et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to the author at the AMITY Institute of Biotechnology, AMITY University Uttar Pradesh Lucknow Campus, UP, India; Tel: 9453141916; E-mail: psrivastava@amity.edu


Abstract

Aims:

To identify most novel drug target and lead molecule for neurodevelopmental disorder Autism, Intellectual Disability (ID) and Attention Deficit Hyperactivity Disorder (ADHD) diseases through system biology approaches

Background:

Neurodevelopmental disorders (NNDs) are disabilities associated chiefly with the functioning of the neurological system and brain. Children with neurodevelopmental disorders have difficulties with speech, behaviour, learning and other neurological functions. Systems biology is a holistic approach to enciphering the complexity of biological systems and their interactions. It opens the way to a more successful discovery of novel therapeutics.

Objective:

To identify most novel drug target and lead molecule for neurodevelopmental disorder Autism, Intellectual Disability (ID) and Attention Deficit Hyperactivity Disorder (ADHD) diseases through system biology approaches.

Methods:

A list of genes was collected from NCBI database for Autism, Intellectual Disability (ID) and Attention Deficit Hyperactivity Disorder (ADHD) diseases. STRING database and Cytoscape software was used for construction and interpreting molecular interaction in the network. 3D structure of target protein, was build and validated.The phytochemicals were identified through various research articles and filtered out by virtual screening through Molinspiration. Molecular docking analyses of known phytochemical with target proteins were performed usingAutoDock tool.

Result:

AKT1 for Autism, SNAP25 for Intellectual Disability (ID) and DRD4 for Attention Deficit Hyperactivity Disorder (ADHD) were identified as most potential drug target through network study. further the modelled structure of obtained target were undergo molecular docking study with kown phytochemicals. Based on lowest binding energy, Huperzine A for Autism and ID, Valerenic acid for ADHD found to be the most potential therapeutic molecules.

Conclusion:

Huperzine A against Autism and ID, Valerenic acid against ADHD found to be the most potential therapeutic molecules and expected to be effective in the treatment of NNDs. Phytochemicals do not have side effects so extract of these can be taken in preventive form too as these disorders occur during developmental stages of the child. Further the obtained molecule if experimentally validated would play promising role for the treatment of NDDs in human.

Keywords: Neurodevelopmental disorder, Autism, Intellectual Disability, Attention Deficit Hyperactivity Disorder, Docking, STRING Database.