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In-silico identification of drug lead molecule against pesticide-exposed neurodevelopmental disorders through the network-based computational model approach

Author(s):

Neha Srivastava, Shifa Ansari and Prachi Srivastava*  

Abstract:


Neurodevelopmental disorders (NDDs) are impairment of the growth and development of the brain or central nervous system, which occurs at the developmental stage. This can include developmental brain dysfunction, which can manifest as neuropsychiatric problems or impaired motor function, learning, language or non-verbal communication. These include the array of disorder, including Autism spectrum disorders (ASD), Attention deficit hyperactivity disorder (ADHD) etc. There is no particular diagnosis and cure for NDDs. These disorders seem to result in a combination of genetic, biological, psychosocial and environmental risk factors. Serval scientific literature reveals the adverse effect of environmental factor specifically, exposure to pesticides which leads to growing number of human pathological conditions; among these, the neurodevelopmental disorder is an emerging issue nowadays. The current study focused on insilico identification of potential drug target for pesticides induced neurodevelopmental disorder including Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) and to design potential drug molecule for the target through drug discovery approaches. We identified 139 candidate genes for ADHD & 206 candidate genes for ASD from the NCBI database for detail study. Protein-protein interaction network analysis was performed to identify key genes/proteins in the network by using STRING 10.0 database and Cytoscape 3.3.0 software. Based on betweenness centrality and node degree as a standard parameter, we identified solute carrier family 6 member 4 (SLC6A4) as a common key protein in both the networks. 3-D structure of the SLC6A4 protein was designed and validated respectively. Molecular docking was performed against twenty-seven possible phytochemicals i.e. beta-amyrin, ajmaline, serpentine, urosolic, huperzine A etc having neuroprotective activity. The best-docked compound was identifying by lowest binding energy (BE). Based on lowest binding energy beta amyrin (B.E = -8.54 kcal/mol) selected as a potential drug candidate. Prediction of drug-likeness & bioactivity analysis of leads was performed by using molinspiration chemoinformatics software that showed drug candidate as a potential inhibitor. Beta amyrin (CID: 73145) was obtained as the most potential therapeutic inhibitor for ASD & ADHD in human.

Keywords:

Autism spectrum disorders (ASD), Attention Deficit Hyperactivity Disorder (ADHD), STRING 10.0, Cytoscape 3.3.0, Molecular docking.

Affiliation:

A.P.J. Abdul Kalam Technical University, Lucknow, UP, AMITY Institute of Biotechnology, AMITY University Uttar Pradesh Lucknow, UP2. AMITY Institute of Biotechnology, AMITY University Uttar Pradesh Lucknow, UP, AMITY Institute of Biotechnology, AMITY University Uttar Pradesh Lucknow, UP2. AMITY Institute of Biotechnology, AMITY University Uttar Pradesh Lucknow, UP



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