Overview

• Researchers used fragment-based and unconstrained AI pipelines incorporating CReM mutations and a fragment-VAE model to generate and computationally screen more than 36 million novel molecules.
• Of the top computational hits, only two molecules could be synthesized and were designated NG1 and DN1 for experimental evaluation.
• NG1 demonstrated potent activity against drug-resistant Neisseria gonorrhoeae in vitro and in mice and was shown to bind LptA, a novel bacterial membrane protein target.
• DN1 cleared methicillin-resistant Staphylococcus aureus skin infections in a mouse model after showing strong antibacterial effects in laboratory cultures.
• Next steps include medicinal chemistry, scale-up of synthesis and preclinical safety studies, with researchers acknowledging challenges in manufacturing, regulatory approval and demonstrating human efficacy.