Pneumolysin inhibitor PB-3 is a specific small molecule inhibitor (pore-blocker) of pneumolysin (PLY), binds to Cys428 adjacent to the cholesterol recognition domain of PLY with KD of 256 nM, block the PLY-induced hemoglobin release in sheep erythrocytes with IC50 of 3.1 uM.
PB-3 shows an IC50 value of 0.22 µM against PLY in presence of 2.5% human serum in the hemolysis assay.
PB-3 (6 uM) exhibits significant concentration-dependent inhibition of PLY and prevented more than 95% of cellular damage in PLY-induced cellular damage in human alveolar epithelial cells (A549 cells).
PB-3 does not inhibit cysteine protease SARS-CoV2 main protease and cysteine-containing protein tyrosine phosphatase PTP1B, as well as perforin.
PB-3 protects human lung cells from wild-type PLY during infection with Streptococcus pneumoniae
PB-3 acts as anti-virulence factor preventing human lung epithelial cells from PLY-mediated cytolysis and cell death during infection with Streptococcus pneumoniae and is active against the homologous Cys-containing CDC perfringolysin (PFO) as well.
Pneumolysin (PLY) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pneumoniae, the main cause for bacterial pneumonia.