AI-Guided Optimization Yields a Potent New HBV Capsid Assembly Modulator
- Starts from known capsid assembly modulator NVR 3-778 and applies a multi-objective optimization workflow combining structure-based fragment growing with medicinal chemistry.
- Machine-learning models are used alongside traditional design to jointly predict antiviral activity and drug-like/ADMET properties.
- The workflow generated and evaluated roughly four dozen novel sulfamoylbenzamide analogs.
- Lead compound 11B-6 emerged with superior antiviral potency and improved drug-like properties versus the starting scaffold.
💡 Points
Forty-some analogs to land one clearly superior lead is a tight design-make-test cycle, and coupling ML-based ADMET prediction to fragment growing off NVR 3-778 is exactly where these models earn their keep — multi-parameter optimization, not potency-chasing alone. Next question: does 11B-6 hold up against the CAM-resistant HBV variants that have dogged this chemotype before.