title: The enterovirus 3C protease inhibitor SG85 efficiently blocks rhinovirus replication and is not cross-resistant with rupintrivir.
abstract: The novel enterovirus protease inhibitor (PI) SG85 effectively inhibits the in vitro replication of 14 rhinoviruses representative of species A and B (median 50% effective concentration, 0.04 μM). A low-level SG85-resistant variant was selected that carried amino acid substitutions S127G and T143A in the 3C protease. Both substitutions are required for low-level resistance to SG85, as demonstrated by reverse genetics. Interestingly, there is no cross-resistance to SG85 and rupintrivir (another PI); a structural explanation is provided for this observation.
authors.affiliation: Laboratory for Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Lacroix
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: Laboratory for Virology, Rega Institute for Medical Research, KU Leuven, 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), Hamburg-Lübeck-Borstel Site, University of Lübeck, Lübeck, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hilgenfeld
authors.affiliation: Laboratory for Virology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium johan.neyts@rega.kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D004770:Enterovirus / Q000187:drug effects / Q000201:enzymology*; D007555:Isoxazoles / Q000494:pharmacology*; D010649:Phenylalanine / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007555:Isoxazoles; D011480:Protease Inhibitors; D011760:Pyrrolidinones; D014764:Viral Proteins; D010649:Phenylalanine; D014633:Valine; C118874:rupintrivir