In silico prediction of drug targets in Vibrio cholerae

Abstract

Identification of potential drug targets is the first step in the process of modern drug discovery, subjected to their validation and drug development. Whole genome sequences of a number of organisms allow prediction of potential drug targets using sequence comparison approaches. Here, we present a subtractive approach exploiting the knowledge of global gene expression along with sequence comparisons to predict the potential drug targets more efficiently. Based on the knowledge of 155 known virulence and their coexpressed genes mined from microarray database in the public domain, 357 coexpressed probable virulence genes for Vibrio cholerae were predicted. Based on screening of Database of Essential Genes using blastn, a total of 102 genes out of these 357 were enlisted as vitally essential genes, and hence good putative drug targets. As the effective drug target is a protein which is only present in the pathogen, similarity search of these 102 essential genes against human genome sequence led to subtraction of 66 genes, thus leaving behind a subset of 36 genes whose products have been called as potential drug targets. The gene ontology analysis using Blast2GO of these 36 genes revealed their roles in important metabolic pathways of V. cholerae or on the surface of the pathogen. Thus, we propose that the products of these genes be evaluated as target sites of drugs against V. cholerae in future investigations.

Bioinformatics-Key to Drug Discovery and Development

“…The number of potential targets for drug discovery process is increasing exponentially. Mining and warehousing of the human genome sequence using bioinformatics has helped to define and classify the nucleotide compositions of those genes, which are responsible for the coding of target proteins, in addition to identifying new targets that offer more potential for new drugs [5,6]. This is an area where the human genome information is expected to play a master role [7].…”

“…These challenges range from high cost of drug discovery to the lengthy and risky trials and approval process, and some time, withdrawal of previously approved drugs from the market and the innovation gap resulting from the dogged quest for blockbuster drugs [1,12,13]. Bioinformatics was widely projected to strengthen the identification of drug targets [6]. The fact that these problems remain mostly unsolved, despite significant bioinformatics investments, is an indication of a larger problem [26,27].…”

Natural compounds for the drug targets of Sexually Transmitted Diseases (STD) using virtual screening

“…One of such approaches is the subtractive genomics that systematically identifies the drug targets by differential genomics [1]. The comparative genomic approach has also been applied to various organisms such as Helicobacter pylori) [2], Toxoplasma gondii [3], Vibrio cholera [4], Mycobacterium leprae [5], Borelia burdorferi [6] and many more studies are underway. Natural compounds of the drug targets of Ureaplasma urealyticum has been studied [7].…”

Role of bioinformatics and pharmacogenomics in drug discovery and development process

“…The number of potential targets for drug discovery process is increasing exponentially. Mining and warehousing of the human genome sequence using bioinformatics has helped to define and classify the nucleotide compositions of those genes, which are responsible for the coding of target proteins, in addition to identifying new targets that offer more potential for new drugs (Chen and Chen 2008;Katara et al 2011). This is an area where the human genome information is expected to play a master role (Yamanishi et al 2010).…”

“…These challenges range from high cost of drug discovery to the lengthy and risky trials and approval process, and some time, withdrawal of previously approved drugs from the market and the innovation gap resulting from the dogged quest for blockbuster drugs (Papanikolaw 1999;Gilbert et al 2003;Klein and Tabarrok 2003;Iskar et al 2012). Bioinformatics was widely projected to strengthen the identification of drug targets (Zemlo 2004;Katara et al 2011). The fact that these problems remain mostly unsolved, despite significant bioinformatics investments, is an indication of a larger problem (Blundell et al 2006;Dhaliwal and Chen 2009;Du and Huang 2012).…”