2. Academic Validation
  3. Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68

Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68

  • Antimicrob Agents Chemother. 2015 Dec;59(12):7782-5. doi: 10.1128/AAC.01375-15.
Liang Sun 1,  Adam Meijer 2,  Mathy Froeyen 3,  Linlin Zhang 4,  Hendrik Jan Thibaut 5,  Jim Baggen 6,  Shyla George 7,  John Vernachio 8,  Frank J M van Kuppeveld 6,  Pieter Leyssen 1,  Rolf Hilgenfeld 4,  Johan Neyts 9,  Leen Delang 1
Affiliations

Affiliations

  • 1 KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
  • 2 Centre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
  • 3 Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, University of Leuven, Leuven, Belgium.
  • 4 Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany German Center for Infection Research (DZIF), University of Lübeck, Lübeck, Germany.
  • 5 KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
  • 6 Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
  • 7 Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany.
  • 8 Biota Pharmaceuticals, Alpharetta, Georgia, USA.
  • 9 KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium [email protected].
PMID: 26369972 DOI: 10.1128/AAC.01375-15
Abstract

We investigated the susceptibility of 10 Enterovirus D68 (EV-D68) isolates (belonging to clusters A, B, and C) to (entero)virus inhibitors with different mechanisms of action. The 3C-protease inhibitors proved to be more efficient than enviroxime and pleconaril, which in turn were more effective than vapendavir and pirodavir. Favipiravir proved to be a weak inhibitor. Resistance to pleconaril maps to V69A in the VP1 protein, and resistance to rupintrivir maps to V104I in the 3C protease. A structural explanation of why both substitutions may cause resistance is provided.

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