Hydantoin: The mechanism of its in vitro anti-enterovirus activity revisited

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 dem...

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Bibliographic Details
Published in:Antiviral research 2016-09, Vol.133, p.106-109
Main Authors: Tijsma, Aloys, Thibaut, Hendrik Jan, Franco, David, Dallmeier, Kai, Neyts, Johan
Format: Article
Language:English
Subjects:
Antiviral Agents - pharmacology
Enterovirus
Enterovirus - drug effects
Humans
Hydantoin
Hydantoins - pharmacology
Morphogenesis
RNA replication
RNA, Viral
Virus Assembly - drug effects
Virus Replication - drug effects
Virus Replication - genetics
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Summary: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. •Hydantoin was earlier reported to solely inhibit enterovirus morphogenesis.•Hydantoin has a dual mechanism of antiviral action that involves inhibition of morphogenesis and RNA replication.•The predominant mechanism of inhibition is determined by the concentration of hydantoin.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2016.07.023