Recent work published in Nature Communications describes the discovery and chemical optimization of small-molecule inhibitors targeting pneumolysin, a key virulence factor of Streptococcus pneumoniae. Starting from an initial hit, medicinal chemistry optimization yielded potent inhibitors that block toxin-induced pore formation and protect human lung epithelial cells from cytolytic damage. The compounds act by targeting a cysteine residue in the cholesterol-binding domain of pneumolysin, establishing this toxin as a tractable target for anti-virulence drug development. 

Link to the paper: Targeted small molecule inhibitors blocking the cytolytic effects of pneumolysin and homologous toxins | Nature Communications