Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
Authors
Aparna Rai
Molecular Informatics and Design Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam India
Vikas Kumar
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD USA
Gaurav Jerath
Molecular Informatics and Design Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam India
C Kartha
Society for Continuing Medical Education & Research, Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala India
Vibin Ramakrishnan
Molecular Informatics and Design Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam India
Advancements in systems biology have resulted in the development of network pharmacology, leading to a paradigm shift from “one-target, one-drug” to “target-network, multi-component therapeutics”. We employ a chimeric approach involving in-vivo assays, gene expression analysis, cheminformatics, and network biology to deduce the regulatory actions of a multi-constituent Ayurvedic concoction, Amalaki Rasayana (AR) in animal models for its effect in pressure-overload cardiac hypertrophy. The proteomics analysis of in-vivo assays for Aorta Constricted and Biologically Aged rat models identify proteins expressed under each condition. Network analysis mapping protein–protein interactions and synergistic actions of AR using multi-component networks reveal drug targets such as ACADM, COX4I1, COX6B1, HBB, MYH14, and SLC25A4, as potential pharmacological co-targets for cardiac hypertrophy. Further, five out of eighteen AR constituents potentially target these proteins. We propose a distinct prospective strategy for the discovery of network pharmacological therapies and repositioning of existing drug molecules for treating pressure-overload cardiac hypertrophy.
Subject terms: Target identification, Clinical pharmacology, Biochemical networks, Cardiology, Cheminformatics
Author Biography
Gaurav Jerath, Molecular Informatics and Design Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam India
PepThera Laboratories Private Limited, Guwahati, Assam India
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