title: Antiviral Activity of Broad-Spectrum and Enterovirus-Specific Inhibitors against Clinical Isolates of Enterovirus D68.
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.
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
authors.forename: Liang
authors.initials: L
authors.lastname: Sun
authors.affiliation: Centre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Adam
authors.initials: A
authors.lastname: Meijer
authors.affiliation: Rega Institute for Medical Research, Laboratory of Medicinal Chemistry, University of Leuven, Leuven, Belgium.
authors.forename: Mathy
authors.initials: M
authors.lastname: Froeyen
authors.affiliation: 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.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Thibaut
authors.affiliation: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jim
authors.initials: J
authors.lastname: Baggen
authors.affiliation: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany.
authors.forename: Shyla
authors.initials: S
authors.lastname: George
authors.affiliation: Biota Pharmaceuticals, Alpharetta, Georgia, USA.
authors.forename: John
authors.initials: J
authors.lastname: Vernachio
authors.affiliation: Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: 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.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hilgenfeld
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium johan.neyts@rega.kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, Leuven, Belgium.
authors.forename: Leen
authors.initials: L
authors.lastname: Delang
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D030016:Enterovirus D, Human / Q000187:drug effects*; D004769:Enterovirus Infections / Q000821:virology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010069:Oxadiazoles / Q000494:pharmacology; D010080:Oxazoles; D011955:Receptors, Drug / Q000737:chemistry / Q000187:drug effects; D012141:Respiratory Tract Infections / Q000821:virology; D014764:Viral Proteins / Q000737:chemistry; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D010069:Oxadiazoles; D010080:Oxazoles; D011955:Receptors, Drug; D014764:Viral Proteins; C115201:pleconaril