Discovery of Ziresovir as a Potent, Selective, and Orally Bioavailable Respiratory Syncytial Virus Fusion Protein Inhibitor.
J Med Chem
; 62(13): 6003-6014, 2019 07 11.
Article
em En
| MEDLINE
| ID: mdl-31194544
Ziresovir (RO-0529, AK0529) is reported here for the first time as a promising respiratory syncytial virus (RSV) fusion (F) protein inhibitor that currently is in phase 2 clinical trials. This article describes the process of RO-0529 as a potent, selective, and orally bioavailable RSV F protein inhibitor and highlights the in vitro and in vivo anti-RSV activities and pharmacokinetics in animal species. RO-0529 demonstrates single-digit nM EC50 potency against laboratory strains, as well as clinical isolates of RSV in cellular assays, and more than one log viral load reduction in BALB/c mouse model of RSV viral infection. RO-0529 was proven to be a specific RSV F protein inhibitor by identification of drug resistant mutations of D486N, D489V, and D489Y in RSV F protein and the inhibition of RSV F protein-induced cell-cell fusion in cellular assays.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Quinazolinas
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Tiazepinas
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Benzazepinas
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Proteínas Virais de Fusão
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Vírus Sincicial Respiratório Humano
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Infecções por Vírus Respiratório Sincicial
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article