RSV entry inhibitor hits fail resynthesis checks, exposing false positives
- Hits from a high-throughput screen for small-molecule RSV entry inhibitors were followed up by resynthesizing the most promising candidates and re-measuring their antiviral activity.
- NMR and LC-MS analysis showed that, for two compound classes, the original screening samples did not match the resynthesized material, pointing to impurities as a possible source of the apparent activity.
- The authors report these false positives to stress rigorous analytical and biological validation and to spare other groups from pursuing non-genuine hits.
💡 Points
Negative results like this save more bench time than most positive papers. When the library sample and the resynthesized compound disagree, suspect a trace impurity or degradation product before the scaffold. In my hands, resynthesis plus NMR and LC-MS would be a hard gate before any SAR is drawn, and unconfirmed entry-inhibitor hits would count as noise.
Validation of Small-Molecule Entry Inhibitors Targeting the Respiratory Syncytial Virus ↗