title: Docking-based virtual screening of known drugs against murE of Mycobacterium tuberculosis towards repurposing for TB.
abstract: Repurposing has gained momentum globally and become an alternative avenue for drug discovery because of its better success rate, and reduced cost, time and issues related to safety than the conventional drug discovery process. Several drugs have already been successfully repurposed for other clinical conditions including drug resistant tuberculosis (DR-TB). Though TB can be cured completely with the use of currently available anti-tubercular drugs, emergence of drug resistant strains of Mycobacterium tuberculosis and the huge death toll globally, together necessitate urgently newer and effective drugs for TB. Therefore, we performed virtual screening of 1554 FDA approved drugs against murE, which is essential for peptidoglycan biosynthesis of M. tuberculosis. We used Glide and AutoDock Vina for virtual screening and applied rigid docking algorithm followed by induced fit docking algorithm in order to enhance the quality of the docking prediction and to prioritize drugs for repurposing. We found 17 drugs binding strongly with murE and three of them, namely, lymecycline, acarbose and desmopressin were consistently present within top 10 ranks by both Glide and AutoDock Vina in the induced fit docking algorithm, which strongly indicates that these three drugs are potential candidates for further studies towards repurposing for TB.
authors.affiliation: Loyola College, Nungambakkam, Chennai - 600034, Tamil Nadu, India.
authors.forename: Sridharan
authors.initials: S
authors.lastname: Brindha
authors.affiliation: National Institute for Research in Tuberculosis (ICMR), Chetpet, Chennai - 600031, Tamil Nadu, India.
authors.forename: Jagadish Chandrabose
authors.initials: JC
authors.lastname: Sundaramurthi
authors.affiliation: Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai - 600025, Tamil Nadu, India.
authors.forename: Devadasan
authors.initials: D
authors.lastname: Velmurugan
authors.affiliation: Loyola College, Nungambakkam, Chennai - 600034, Tamil Nadu, India.
authors.forename: Savariar
authors.initials: S
authors.lastname: Vincent
authors.affiliation: Loyola College, Nungambakkam, Chennai - 600034, Tamil Nadu, India.
authors.forename: John Joel
authors.initials: JJ
authors.lastname: Gnanadoss
keywords: Bioinformatics; Drugs; Repurposing; Tuberculosis; Virtual Screening; murE