Researchers created nelfinavir-like compounds that stopped Streptococcus pyogenes bacteria from producing the streptolysin S (SLS) toxin, an important virulence factor during infection. The study appears in the journal ACS Chemical Biology.
Nelfinavir, an HIV protease inhibitor, targets not only HIV protein but also a critical enzyme that is related to one in S. pyogenes involved in producing SLS. For the study, scientists synthesized 57 nelfinavir analogs, resulting in a series of compounds with improved anti-SLS activity. The inhibition was shown in live S. pyogenes cells and through in vitro protease inhibition assays. Nelfinavir was also found to inhibit the maturation of other azole-containing products, including listeriolysin S, clostridiolysin S, and plantazolicin production.
Researchers conclude that the nelfinavir and its variants may help better understand the protelysis in SLS maturation and help with future research in SLS biosynthesis.
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