De Novo Macrocyclic Peptide Inhibitors of Hepatitis B Virus Cellular Entry.
Cell Chem Biol
; 25(7): 906-915.e5, 2018 07 19.
Article
em En
| MEDLINE
| ID: mdl-29779957
ABSTRACT
Hepatitis B virus (HBV) constitutes a significant public health burden, and currently available treatment options are not generally curative, necessitating the development of new therapeutics. Here we have applied random non-standard peptide integrated discovery (RaPID) screening to identify small macrocyclic peptide inhibitors of HBV entry that target the cell-surface receptor for HBV, sodium taurocholate cotransporting polypeptide (NTCP). In addition to their anti-HBV activity, these molecules also inhibit cellular entry by the related hepatitis D virus (HDV), and are active against diverse strains of HBV (including clinically relevant nucleos(t)ide analog-resistant and vaccine escaping strains). Importantly, these macrocyclic peptides, in contrast to other NTCP-binding HBV entry inhibitors, exhibited no inhibition of NTCP-mediated bile acid uptake, making them appealing candidates for therapeutic development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Peptídeos
/
Vírus da Hepatite B
/
Receptores de Superfície Celular
/
Compostos Macrocíclicos
Limite:
Humans
Idioma:
En
Revista:
Cell Chem Biol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão