Assessing In Vitro Resistance Development in Enterovirus A71 in the Context of Combination Antiviral Treatment.
ACS Infect Dis
; 7(10): 2801-2806, 2021 10 08.
Article
em En
| MEDLINE
| ID: mdl-34529400
ABSTRACT
There are currently no antivirals available to treat infection with enterovirus A71 (EV-A71) or any other enterovirus. The extensively studied capsid binders rapidly select for drug-resistant variants. We here explore whether the combination of two direct-acting enterovirus inhibitors with a different mechanism of action may delay or prevent resistance development to the capsid binders. To that end, the in vitro dynamics of resistance development to the capsid binder pirodavir was studied either alone or in combination with a viral 2C-targeting compound (SMSK_0213), a viral 3C-protease inhibitor (rupintrivir) or a viral RNA-dependent RNA polymerase inhibitor (7DMA). We demonstrate that combining pirodavir with either rupintrivir or 7DMA delays the development of resistance to pirodavir and that no resistance to the protease or polymerase inhibitor develops. The combination of pirodavir with the 2C inhibitor results in a double-resistant virus population, where only the minority carries the resistant mutation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enterovirus
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Enterovirus Humano A
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Infecções por Enterovirus
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article