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

Abstract

MotivationRepurposing of known drugs to newer clinical conditions is a promising avenue for finding novel therapeutic applications for tuberculosis. MethodsWe 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. ResultsWe 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. ConclusionOur results suggest that lymecycline and cefpodoxime have potential to be repurposed for the treatment of tuberculosis.

Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade

“…The involvement of Minocycline in inhibiting sonic hedgehog–patched–gli signaling was also reported in the same study . In another study Lymecycline (10 μg/mL) alone and in combination of Isoniazid (0.2 μg/mL) and Rifampin (2 μg/mL) substantially inhibited M.tb growth by 93.47%, 99.25%, and 98.35%, respectively, with trpD as a potential drug target . TrpD encodes an enzyme probable anthranilate phosphoribosyl transferase, required for the tryptophan amino acid biosynthesis pathway .…”

“… 42 In another study Lymecycline (10 μg/mL) alone and in combination of Isoniazid (0.2 μg/mL) and Rifampin (2 μg/mL) substantially inhibited M.tb growth by 93.47%, 99.25%, and 98.35%, respectively, with trpD as a potential drug target. 43 TrpD encodes an enzyme probable anthranilate phosphoribosyl transferase, required for the tryptophan amino acid biosynthesis pathway. 44 Doxycycline was recently identified as a successful adjunctive host directed therapy (HDT) in controlling TB-associated tissue degradation caused by matrix metalloproteinases (MMPs) in Phase II trial research, and the drug is also advised for further larger investigations.…”