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.

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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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