In vitro and in vivo efficacy of a novel nucleoside analog H44 against Crimean-Congo hemorrhagic fever virus.
Antiviral Res
; 199: 105273, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-35257725
Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne virus that causes fever, hemorrhage, and multi-organ failure, with an average fatality rate of â¼40% in humans. Currently, there are no available vaccines or drugs for the treatment of Crimean-Congo hemorrhagic fever (CCHF). Favipiravir (T-705), a nucleoside analog, protects against CCHFV infection in animal models. Here, we evaluated the anti-CCHFV efficacy of several nucleoside analogs, including some well-known compounds such as remdesivir (GS-5734), EIDD-1931 and its prodrug molnupiravir (EIDD-2801), as well as a novel T-705-derived compound H44. T-705, H44, and EIDD-1931 inhibited CCHFV infection in vitro while GS-5734 had no inhibitory effect. All three nucleoside analogs functioned at the "post-entry" stage of virus infection. However, EIDD-2801 failed to protect type I interferon receptor knockout (IFNAR)-/- mice from CCHFV infection. H44, similar to T-705, conferred 100% protection to IFNAR-/- mice against lethal CCHFV challenge, even with delayed administration. This study provided in vitro and in vivo data regarding the anti-CCHFV efficacy of different nucleosides and identified a novel compound, H44, as a promising drug candidate for the treatment of CCHFV infection in vivo.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Febre Hemorrágica da Crimeia-Congo
/
Febre Hemorrágica da Crimeia
Limite:
Animals
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Holanda