Small Molecule Agonists for the Type I Interferon Receptor: An In Silico Approach.
J Interferon Cytokine Res
; 36(3): 180-91, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26700737
ABSTRACT
Type I interferons (IFNs) exhibit broad-spectrum antiviral activity, with potential utility against emerging acute virus infections that pose a threat to global health. Recombinant IFN-αs that have been approved for clinical use require cold storage and are administered through intramuscular or subcutaneous injection, features that are problematic for global distribution, storage, and administration. Cognizant that the biological potency of an IFN-α subtype is determined by its binding affinity to the type I IFN receptor, IFNAR, we identified a panel of small molecule nonpeptide compounds using an in silico screening strategy that incorporated specific structural features of amino acids in the receptor-binding domains of the most potent IFN-α, IFN alfacon-1. Hit compounds were selected based on ease of synthesis and formulation properties. In preliminary biological assays, we provide evidence that these compounds exhibit antiviral activity. This proof-of-concept study validates the strategy of in silico design and development for IFN mimetics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Interferon-alfa
/
Vírus da Encefalomiocardite
/
Receptor de Interferon alfa e beta
/
Bibliotecas de Moléculas Pequenas
/
Peptidomiméticos
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article