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An in silico target‐specific drug repurposing approach for autism
Author(s) -
Marisse Lakshmi Prasanna,
Sree G.N.S. Hema,
Rajalekshmi Saraswathy Ganesan
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043521
Subject(s) - autism , drug repositioning , in silico , gene , computational biology , druggability , bioinformatics , biology , medicine , psychology , genetics , drug , developmental psychology , psychiatry
Abstract Background Autism a most disabling heterogenous neuro‐developmental disorder with vast heritability is exemplified by impaired social interaction, communication, motor function, cognition, restricted and repetitive stereotyped behaviors. The inability to identify risk factors and genetic variants associated with the pathogenesis has attributed to its complexity. The current research of autism is only focused on symptomatic relief rather than cure. This dearth in research for specific drugs aids in unwinding druggable targets via drug repurposing. Method The GEO dataset GSE22507 from National Centre for Biotechnology Information (NCBI) comprising the microarray data of 67 autistic children and 47 controls was selected. Increasing paternal age, an established risk factor for the development of autism was later considered for computing the median age of fathers in to young fathers, old fathers and total age. This data was analyzed through Geo2 Enrichr for retrieving significant differential expressed genes (DEG’s) which were processed for functional enrichment analysis though Database for Annotation Visualization and Integrated Discovery tool. Subsequently, protein‐protein interactions were constructed between DEG’s and literature derived genes using Search Tool for Retrieval of Interacting Genes. The common genes amongst the groups were identified and considered as potential targets. Selected targets and their respective drugs acquired from FDA were subjected to molecular docking studies through Extra Precision (XP) mode in Glide tool of Schrodinger drug design suite (version 10.7). The shortlisted targets were ranked and evaluated to energy calculations via MM‐GBSA. Result Protein‐protein interaction for all the groups revealed FOS a proto‐oncogene as the potential target. Drugs that are found to possess the best docking score and glide energy were further subjected to MM‐GBSA studies. Compounds exhibiting top binding free energies (∆G) i.e., ‐60 k.cal/mol are selected for literature survey. This survey revealed the affinity of 6 drugs namely, Pranlukast, Bemotrizinol, Ceforanid, Dasabuvir, Flavin Adenine Dinucleotide drugs. These drugs were not reported in literature for autism. Conclusion The FOS target should be validated further along with the aforementioned drugs in in vitro and in vivo to identify potential targets for a devastating disease like autism.