2. Academic Validation
  3. A robust cell-based infection model for Rhinovirus C research and antiviral drug discovery

A robust cell-based infection model for Rhinovirus C research and antiviral drug discovery

  • Npj Viruses. 2026 May 11. doi: 10.1038/s44298-026-00194-5.
Heyrhyoung Lyoo 1,  Yeranddy A Alpizar 2,  Céline Sablon 1,  Toon Röpke 1,  Jasmine Paulissen 1,  Madina Rasulova 1,  Nathalie Thys 1,  Chang-Soo Yun 3,  Nam-Chul Cho 4,  Kai Dallmeier 2,  Pieter Leyssen 5,  Soo-Bong Han 3 6 7,  Johan Neyts 8 9,  Hendrik Jan Thibaut 10
Affiliations

Affiliations

  • 1 Translational Platform for Virus, Vaccine and Cancer Research (TPVC), Virology, Antiviral Drug and Vaccine Research Group, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • 2 Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), Virology, Antiviral Drug and Vaccine Research Group, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • 3 Therapeutics and Biotechnology Division, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
  • 4 Drug Information Platform Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
  • 5 Caps-It, Virology, Antiviral Drug and Vaccine Research Group, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
  • 6 Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon, Republic of Korea.
  • 7 School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
  • 8 Laboratory of Virology & Antiviral Research (AntiVir), Virology, Antiviral Drug and Vaccine Research Group, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. [email protected].
  • 9 VirusBank Platform, Virology, Antiviral Drug and Vaccine Research Group, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. [email protected].
  • 10 Translational Platform for Virus, Vaccine and Cancer Research (TPVC), Virology, Antiviral Drug and Vaccine Research Group, Rega Institute, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. [email protected].
PMID: 42108281 DOI: 10.1038/s44298-026-00194-5
Abstract

Rhinoviruses (RV) comprise three species, RV-A, RV-B, and RV-C, with approximately 170 types. RV-C is associated with severe respiratory illness, particularly in children and individuals with asthma or chronic obstructive pulmonary disease, underscoring the need for effective Antiviral strategies. Progress in RV-C research and drug discovery has been limited by the lack of robust, scalable cell-based Infection models that recapitulate the complete RV-C replication cycle. Here, we describe a high-content imaging (HCI)-based high-throughput Infection system for RV-C. Rather than relying solely on receptor overexpression, we used a genetically stable fluorescent reporter virus (RV-C15a-mGL) to screen ~300 monoclonal cell lines expressing the RV-C receptor variant CDHR3-Tyr529. This approach identified a clone that efficiently supports RV-C replication and revealed that productive Infection depends on determinants beyond receptor abundance alone. Using this clone, we established and validated a robust, scalable screening platform with Z' > 0.75 in both 96- and 384-well formats. The system was readily adapted to additional RV-C types (C11 and C41), as well as RV-A and RV-B. A pilot screen of approximately 10,000 small molecules identified both known and novel RV-C inhibitors, supporting the utility of this platform for Antiviral discovery and for advancing the study of RV-C biology.

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