Optimised benzothiophenes block Mtb virulence by inhibiting the MprB histidine kinase
- The earlier hit BTP15 protects host cells from Mtb-induced death by blocking phagosomal escape through MprB inhibition, but had poor pharmacokinetics.
- New benzothiophene analogues were screened for MprB inhibition, microsomal stability, toxicity and ex vivo efficacy in THP-1 and MRC-5 cells.
- The aim is a virulence-blocking route that avoids killing the bacterium directly, which may reduce resistance pressure.
💡 Points
Antivirulence is attractive on paper, but the hard part is demonstrating efficacy without a bactericidal readout. I'd look hardest at whether the stability gains translate into in vivo exposure, since BTP15's problem was PK, and at whether MprB engagement is shown cleanly in the infected-cell setting.