title: The capsid binder Vapendavir and the novel protease inhibitor SG85 inhibit enterovirus 71 replication.
abstract: Antivirals against enterovirus 71 (EV71) are urgently needed. We demonstrate that the novel enteroviral protease inhibitor (PI) SG85 and capsid binder (CB) vapendavir efficiently inhibit the in vitro replication of 21 EV71 strains/isolates that are representative of the different genogroups A, B, and C. The PI rupintrivir, the CB pirodavir, and the host-targeting compound enviroxime, which were included as reference compounds, also inhibited the replication of all isolates. Remarkably, the CB compound pleconaril was devoid of any anti-EV71 activity. An in silico docking study revealed that pleconaril-unlike vapendavir and pirodavir-lacks essential binding interactions with the viral capsid. Vapendavir and SG85 (or analogues) should be further explored for the treatment of EV71 infections. The data presented here may serve as a reference when developing yet-novel inhibitors.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Aloys
authors.initials: A
authors.lastname: Tijsma
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Franco
authors.affiliation: Biota Pharmaceuticals Inc., Notting Hill, Vic., Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Tucker
authors.affiliation: Institute of Biochemistry, Center for Structural and Cell Biology in Medicine, University of Lübeck, Lübeck, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Hilgenfeld
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Mathy
authors.initials: M
authors.lastname: Froeyen
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Leyssen
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium johan.neyts@rega.kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D002213:Capsid / Q000187:drug effects; D036022:Capsid Proteins / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics; D029821:Enterovirus A, Human / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D004769:Enterovirus Infections / Q000188:drug therapy / Q000821:virology; D007555:Isoxazoles / Q000494:pharmacology; D062105:Molecular Docking Simulation; D010091:Oximes; D010649:Phenylalanine / Q000031:analogs & derivatives; D010880:Piperidines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D011724:Pyridazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D013449:Sulfonamides; D014633:Valine / Q000031:analogs & derivatives; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D036022:Capsid Proteins; D007555:Isoxazoles; D010091:Oximes; D010880:Piperidines; D011480:Protease Inhibitors; D011724:Pyridazines; D011760:Pyrrolidinones; D013449:Sulfonamides; D010649:Phenylalanine; C074589:pirodavir; D014633:Valine; C021595:viroxime; C118874:rupintrivir