title: Structure-Based Targeting of Orthologous Pathogen Proteins Accelerates Antiparasitic Drug Discovery.
abstract: Parasitic diseases caused by eukaryotic pathogens impose significant health and economic burden worldwide. The level of research funding available for many parasitic diseases is insufficient in relation to their adverse social and economic impact. In this article, we discuss that extant 3D structural data on protein-inhibitor complexes can be harnessed to accelerate drug discovery against many related pathogens. Assessment of sequence conservation within drug/inhibitor-binding residues in enzyme-inhibitor complexes can be leveraged to predict and validate both new lead compounds and their molecular targets in multiple parasitic diseases. Hence, structure-based targeting of orthologous pathogen proteins accelerates the discovery of new antiparasitic drugs. This approach offers significant benefits for jumpstarting the discovery of new lead compounds and their molecular targets in diverse human, livestock, and plant pathogens.
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) , Aruna Asaf Ali Road, New Delhi 110067, India.
authors.forename: Vitul
authors.initials: V
authors.lastname: Jain
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) , Aruna Asaf Ali Road, New Delhi 110067, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) , Aruna Asaf Ali Road, New Delhi 110067, India.
authors.forename: Gajinder
authors.initials: G
authors.lastname: Singh
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) , Aruna Asaf Ali Road, New Delhi 110067, India.
authors.forename: Manickam
authors.initials: M
authors.lastname: Yogavel
authors.affiliation: Molecular Medicine Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) , Aruna Asaf Ali Road, New Delhi 110067, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology; D062126:Databases, Chemical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D010272:Parasitic Diseases / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000977:Antiparasitic Agents; D004791:Enzyme Inhibitors
keywords: drug discovery; parasitic diseases; structural biology