title: Hydantoin: The mechanism of its in vitro anti-enterovirus activity revisited.
abstract: It has been generally accepted that hydantoin [5-(3,4-dichlorophenyl)methylhydantoin] exerts its anti-enterovirus activity by solely inhibiting viral assembly. However, we here show that hydantoin inhibits enteroviral RNA synthesis as well as subgenomic replication in a dose-dependent manner. We demonstrate that inhibition of RNA synthesis is the predominant mechanism of action at relatively high concentrations of hydantoin. However, at lower concentrations inhibition of viral morphogenesis is the main mechanism of action. Thus, hydantoin inhibits enteroviral replication by two distinct mechanisms.
authors.affiliation: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium.
authors.forename: Aloys
authors.initials: A
authors.lastname: Tijsma
authors.affiliation: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium.
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Thibaut
authors.affiliation: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Franco
authors.affiliation: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium.
authors.forename: Kai
authors.initials: K
authors.lastname: Dallmeier
authors.affiliation: Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, University of Leuven, Leuven, Belgium. Electronic address: johan.neyts@kuleuven.be.
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D004770:Enterovirus / Q000187:drug effects*; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology*; D012367:RNA, Viral; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D006827:Hydantoins; D012367:RNA, Viral
keywords: Enterovirus; Hydantoin; Morphogenesis; RNA replication