Validation of Small-Molecule Entry Inhibitors Targeting the Respiratory Syncytial Virus.
9 affiliations
- 1Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) - Helmholtz Centre for Infection Research (HZI), Department of Pharmacy, Saarland University, Saarbrücken, Germany.
- 2TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture Between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
- 3PharmaScienceHub (PSH), Saarland University, Saarbrücken, Germany.
- 4Medizinische Hochschule Hannover-Institut für Virologie, MHH, Hannover, Germany.
- 5Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- 6German Centre for Infection Research, Partner Site Hamburg-Borstel-Lübeck-Riems, Hamburg, Germany.
- 7Institute for Molecular Virology and Tumorvirology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
- 8German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover, (BREATH), Hannover, Germany.
- 9Cluster of Excellence RESIST (EXC 2155), Hanover Medical School, Hannover, Germany.
Abstract
Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections worldwide, particularly in infants, young children, and elderly individuals. Despite the availability of preventive options such as vaccines and monoclonal antibodies, effective antiviral therapies for acute infections remain limited. Therefore, we investigated small-molecule entry inhibitors identified in a high-throughput campaing and evaluated the most promising candidates in detail by performing resynthesis and determining their antiviral activity. Unfortunately, analytical investigations by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) revealed discrepancies between the screening samples and the resynthesized compounds for two compound classes, highlighting the complexity of hit validation and the potential influence of impurities. By publishing these results, we aim not only to underscore the importance of rigorous analytical and biological validation in screening campaigns but also to support the development of improved strategies for identifying reliable RSV inhibitors. We also believe it is important to publish false-positive hits to avoid time efforts on projects that assume such compounds as genuine hits.
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BibTeX
@article{karhan2026validation,
title = {{Validation of Small-Molecule Entry Inhibitors Targeting the Respiratory Syncytial Virus.}},
author = {Christina Karhan and Svenja M Sake and Melanie Urbanek-Quaing and Diletta Bergamo and Jessica Rückert and Jiabin Huang and Christina Grethe and Antonia P Gunesch and Anne Kühnel and Birthe Reinecke and Nicole Fischer and Thomas F Schulz and Thomas Pietschmann and Anna K H Hirsch},
journal = {ChemMedChem},
year = {2026},
month = oct,
doi = {10.1002/cmdc.70501},
url = {https://europepmc.org/article/MED/42908255},
note = {CC BY},
}
RIS
TY - JOUR
TI - Validation of Small-Molecule Entry Inhibitors Targeting the Respiratory Syncytial Virus.
AU - Christina Karhan
AU - Svenja M Sake
AU - Melanie Urbanek-Quaing
AU - Diletta Bergamo
AU - Jessica Rückert
AU - Jiabin Huang
AU - Christina Grethe
AU - Antonia P Gunesch
AU - Anne Kühnel
AU - Birthe Reinecke
AU - Nicole Fischer
AU - Thomas F Schulz
AU - Thomas Pietschmann
AU - Anna K H Hirsch
PY - 2026
DA - 2026/10/01
JO - ChemMedChem
DO - 10.1002/cmdc.70501
UR - https://europepmc.org/article/MED/42908255
AB - Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections worldwide, particularly in infants, young children, and elderly individuals. Despite the availability of preventive options such as vaccines and monoclonal antibodies, effective antiviral therapies for acute infections remain limited. Therefore, we investigated small-molecule entry inhibitors identified in a high-throughput campaing and evaluated the most promising candidates in detail by performing resynthesis and determining their antiviral activity. Unfortunately, analytical investigations by nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) revealed discrepancies between the screening samples and the resynthesized compounds for two compound classes, highlighting the complexity of hit validation and the potential influence of impurities. By publishing these results, we aim not only to underscore the importance of rigorous analytical and biological validation in screening campaigns but also to support the development of improved strategies for identifying reliable RSV inhibitors. We also believe it is important to publish false-positive hits to avoid time efforts on projects that assume such compounds as genuine hits.
SN - 1860-7179
SN - 1860-7187
ER -