RSV entry-inhibitor screening hits fail resynthesis checks
- Resynthesized RSV entry-inhibitor hits from a high-throughput screen were re-tested for antiviral activity.
- NMR and LC-MS revealed that screening samples differed from resynthesized material in two compound classes, implicating impurities.
- The authors publish these false positives to encourage rigorous analytical and biological validation and spare others wasted effort.
💡 Points
Classic HTS trap: when two scaffold classes lose activity on resynthesis, I'd bet on a trace reactive or metal-laden impurity, not a real SAR cliff. Entry-inhibitor chemotypes also tend to be lipophilic and aggregation-prone, so I'd treat any new entry hit as suspect until resynthesized material and an orthogonal assay agree.
Validation of Small‐Molecule Entry Inhibitors Targeting the Respiratory Syncytial Virus ↗