In silico and in vitro screening of FDA-approved drugs for potential repurposing against tuberculosis

Brindha, S.; Sundaramurthi, J. C.; Vincent, S.; Velmurugan, D.; Gnanadoss, J. J.

doi:10.1101/228171

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bioRxiv · 10.1101/228171

In silico and in vitro screening of FDA-approved drugs for potential repurposing against tuberculosis

Brindha, S.·Sundaramurthi, J. C.·Vincent, S.·Velmurugan, D.·Gnanadoss, J. J.

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Abstract

MotivationRepurposing of known drugs to newer clinical conditions is a promising avenue for finding novel therapeutic applications for tuberculosis.\n\nMethodsWe performed docking-based virtual screening for 1554 known drugs against two of the potential drug targets, namely trpD and coaA of M. tuberculosis. In the first round of in silico screening we used rigid docking using Glide and AutoDock Vina. We subjected the consistently ranked drugs for induced-fit docking by these tools against the same target proteins. We performed luciferase reporter phage (LRP) assay to determine the biological activity of five selected drugs against M. tuberculosis.\n\nResultsWe observed lymecycline and cefpodoxime to be active against drug susceptible and drug resistant strains of M. tuberculosis. In addition, lymecycline and cefpodoxime showed synergistic activity with rifampin and isoniazid against M. tuberculosis.\n\nConclusionOur results suggest that lymecycline and cefpodoxime have potential to be repurposed for the treatment of tuberculosis.

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Brindha, S., Sundaramurthi, J. C., Vincent, S., Velmurugan, D., Gnanadoss, J. J.. 2017-12-03. In silico and in vitro screening of FDA-approved drugs for potential repurposing against tuberculosis. https://doi.org/10.1101/228171

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