Virtual screening and evaluation of Ketol-Acid Reducto-Isomerase (KARI) as a putative drug target for Aspergillosis

Various reports from the past two decades point to the occurrence of invasive fungal infections have been greater than ever. Aspergillus represents a huge genus of economically, as well as ecologically, important fungi in industry and many fields of applied and clinical research. Aspergilli are also a leading cause of fungal morbidity and mortality in immune compromised patients [1-6]. Clinically accessible antifungal agents have quite a few downsides such as restricted potency and spectrum, non-optimal pharmacokinetics, severe resistance and drug-related toxicity. There is an emergent need to develop new antifungal drugs with a new chemical composition and novel mechanism of action [7]. Active efforts are being made by several international agencies and pharmaceutical majors to identify the drug targets and develop new drugs to treat these diseases effectively. To identify an antifungal drug targets for Aspergilli is required to develop new pharmaceuticals, to meet the challenge. Metabolic variations among organisms may be oppressive for the targets for pathogen such as Aspergilli. Because of the huge similarity among Metabolism and enzymes with host, Eukaryotic pathogens such as Aspergilli are always being tedious to control. The information about pathogen and host and their interaction are recurring deposited. A huge database for metabolome, proteome and genome are available, which may exploit for targeting some enzyme, which could be a server for drug designing [7,8]. The KARI has been considered as a target for this study as a result of comparative pathway analysis between host and parasite [8]. This enzyme is involve in biosynthesis of branched chain amino acid (Valine, leucine, isoleucine), Pantothenate and CoA in Aspergillus. KARI catalyzes the conversion (s)-2 Aceto-2 hydroxybutanoate to (R)-3-hydroxy 3- methyl 2-oxopentanoate and again KARI utilizes this substrate and produces (R) 2,3-dihydroxy-3-methylpentanoate and converted it into Lucine and Isolucine