A penicillin-binding protein inhibitor series to target drug-resistant Neisseria gonorrhoeae - PubMed
4 hours ago
- #penicillin-binding protein inhibitor
- #gonorrhoea
- #drug resistance
- Researchers developed a new series of benzoxaborinine-based penicillin-binding protein inhibitors (boro-PBPi) to combat drug-resistant Neisseria gonorrhoeae, specifically targeting strains with altered penA alleles that threaten ceftriaxone efficacy.
- The optimized compound 21 (VNRX-14079) showed potent antibacterial activity against multidrug-resistant N. gonorrhoeae by binding covalently via its boron atom to the PBP2 catalytic residue Ser310, with structural studies highlighting the importance of β3-β4 loop mobility for improved affinity.
- Boro-PBPi 21 demonstrated bactericidal activity, a low frequency of resistance, a good safety profile, suitable pharmacokinetics, and in vivo efficacy in a mouse infection model against ceftriaxone-resistant N. gonorrhoeae, positioning it as a promising antigonorrhoea agent for further development.