Docking screen of approved drugs flags saquinavir and raltegravir as ClpP1-directed anti-TB leads
- Approved drugs were docked into the S1 pocket of the Mycobacterium tuberculosis ClpP1 crystal structure, with saquinavir and raltegravir ranking best.
- Long molecular dynamics runs suggested both stay stably bound in the pocket.
- Both showed concentration-dependent growth inhibition of an avirulent M. tuberculosis strain in vitro, with saquinavir stronger; target engagement was not directly shown, so mechanism and preclinical work remain open.
💡 Points Based on the abstract
Docking rank plus a stable MD trajectory is cheap, and neither shows binding. Whole-cell growth inhibition fits many explanations besides ClpP1. A biochemical ClpP1 activity or direct binding assay is the obvious next step, ideally with a docked-but-low-ranked drug as a negative control.