A novel promising therapeutic option against hepatitis C virus: an oral nucleotide NS5B polymerase inhibitor sofosbuvir.
Curr Med Chem
; 20(30): 3733-42, 2013.
Article
em En
| MEDLINE
| ID: mdl-23848533
ABSTRACT
Hepatitis C virus (HCV) infection is one of the main causes of liver disease worldwide. Its treatment is currently based on the combination of peg-interferon, ribavirin, and, for patients with genotype 1, a protease inhibitor (telaprevir or boceprevir). However, interferon-based combinations are not effective in all patients. Moreover, they are contraindicated in patients who cannot receive interferon (e.g. those with decompensated cirrhosis), and are frequently associated with adverse events. Consequently, there is a need to develop new drugs to treat HCV infection. This review focuses on preclinical and clinical data regarding sofosbuvir (GS-7977), a uridine nucleotide analogue inhibitor of HCV NS5 B polymerase that is effective against HCV genotypes 1,2, 3,4 and 6. Thanks to its excellent pharmacokinetic profile, sofosbuvir can be administered in an oral single daily dose. In vitro it exerts a potent antiviral effect against HCV. Clinical data show that combined with peg-interferon and ribavirin for 12 weeks it yields SVR of about 90% in subjects with HCV genotype 1 and about 100% in patients with HCV genotype 2 or 3. Moreover, sofosbuvir and ribavirin administered for 12 weeks yield similar high SVR rate (84% for genotype 1 and 100% for genotype 2/3 patients) as well as sofosbuvir and daclatasvir (an inhibitor of NS5A) which produce SVR rate of about 100% regardless of genotype or of ribavirin employment. Safety and tolerability of sofosbuvir appear to be excellent. In conclusion, sofosbuvir especially in interferon-free combinations represents a very promising option in the treatment of chronic hepatitis C.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Uridina Monofosfato
/
RNA Polimerases Dirigidas por DNA
/
Proteínas não Estruturais Virais
/
Hepacivirus
/
Inibidores Enzimáticos
Limite:
Humans
Idioma:
En
Revista:
Curr Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Itália