Endocannabinoid CB1 antagonists as hepatitis C virus antivirals

Ref: 13067
A novel class of agents, the second-generation CB1 antagonists, have demonstrated a strong antiviral effect against the hepatitis C virus.

Key advantages
  • A novel class of oral antiviral agents
  • Cause rapid reduction in HCV viral replication in vitro
  • Target the host:
    • Likely to be effective against all Hepatitis C genotypes
    • Low risk of viral resistance

Background

Chronic Hepatitis C affects over 200 million people worldwide and is a leading cause of cirrhosis, liver cancer and health related morbidity. Current antiviral therapy with Pegylated interferon and ribavirin leads to virus eradication in only ~50% of cases.

The addition of protease and polymerase inhibitors to standard therapy has been associated with resistance issues, significant side effects and is likely to increase eradication rates by just 10-20%. It is clear therefore that better treatments are required.

The invention

This invention involves the use of a novel class of agents as treatment for Hepatitis C. These agents have not previously been known to target the hepatitis C virus and are unrelated to protease, polymerase or NS5A inhibitors.

They are a small molecule and can be delivered in oral form. These agents reduce viral replication by over 90% in a hepatitis C virus cell culture model, following a single dose. Because these agents target the host, rather than the virus, there is little risk of resistance and the treatments are likely to be effective for all genotypes of hepatitis C.

Applications

These agents could be used in combination with current antiviral therapy to provide rapid reduction in viral load and an increased rate of sustained virological response in Hepatitis C. They may also be useful as sole therapy or in combination with other oral antivirals in patients with advanced disease who cannot tolerate interferon based therapy.

Principal inventors

  • Dr David van der Poorten
  • Dr Mark Douglas
  • Professor Jacob George

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