Thiosialoside-decorated polymers use a two-step mechanism to inhibit both early and late stages of influenza virus infection.
Eur J Med Chem
; 199: 112357, 2020 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-32428793
ABSTRACT
We describe the preparation of thiosialoside-modified poly (methyl vinyl ether-alt-maleic anhydride) as second-generation polymeric conjugates for the inhibition of influenza virus infection. These synthetic glycopolymers show significantly enhanced neuraminidase inhibitory and antiviral activity in enzyme and cellular levels, respectively. The polyvalent thiosialosides also exhibit comparable inhibitory activity to the first-line anti-influenza drugs Zanamivir® and Oseltamivir® against the PR8 influenza virus strain in virus growth inhibition assays, which may be attributed to multivalent binding to neuraminidase on the virion particles, leading to the virion aggregation and further inhibiting the attaching/fusion and releasing steps in the influenza virus life-cycle. These findings suggest that attaching monomeric sialoside with neuraminidase inhibitory activity to a polymeric scaffold will synergistically disturb both the early and late stages of influenza virus infection, and provides a basis for the development of efficacious anti-viral agents against both wild-type and drug-resistant mutant strains.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
/
Virus de la Influenza A
/
Polímeros
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Ácidos Siálicos
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Tioglicósidos
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Infecciones por Orthomyxoviridae
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2020
Tipo del documento:
Article
País de afiliación:
China