ContraVir Reports New Mechanism of Action for Hepatitis B Virus Inhibitor CRV431

ContraVir Reports New Mechanism of Action for Hepatitis B Virus Inhibitor CRV431

ContraVir Pharmaceuticals, a New Jersey-based biopharma company that develops and commercializes antiviral therapies, is providing new insights into the mechanism of action of its hepatitis B virus (HBV)-optimized cyclophilin inhibitor CRV431.

New studies show that CRV431 potently blocks the interaction between hepatitis B surface antigen (HBsAg), a key HBV protein, and cyclophilin A, an important cellular protein, according to a company press release. ContraVir says this new information could explain previous findings that CRV431 reduces HBsAg in many experimental systems. High levels of HBsAg in HBV-infected patients make it likely that a patient’s hepatitis B will lead to liver fibrosis, cirrhosis and cancer.

In previous studies by the team of Philippe Gallay, PhD, of the Scripps Research Institute, ContraVir had reported that CRV431 blocked the interaction between HBV X protein (HBx) and cyclophilin A. HBx is vital for the virus life cycle, particularly to maintain its replication inside liver cells and for disease progression.

HBsAg fell in several experimental settings after CRV431 was given. These new results point to a much broader action of the inhibitor, as it affects other crucial viral proteins and ultimately support ContraVir’s goal for finding a “functional cure” — to suppress HBV even after patients finish treatment. To achieve this, ContraVir plans to fight HBV by combining drugs with complementary modes of actions.

Tenofovir Exalidex (TXL), the company vehicle for delivering high concentrations of the active antiviral agent Viread (tenofovir), lowers the load of viruses in the blood. Administering CRV431 could therefore complement TXL’s activity by targeting key viral proteins, including HBsAg, which will increase the immune system’s chances of getting rid of the viral particles.

“The goal of HBV drug research is to eradicate the virus, so that patients no longer have to worry about the long-term consequences of infection,” said Robert Foster, Pharm.D., PhD, the company’s chief scientific officer.

“Our finding that CRV431 targets hepatitis B surface antigen is promising because reducing or eradicating surface antigen is considered an important step in combating HBV,” said Foster. “Combination therapy with CRV431 and tenofovir exalidex, with their distinct and complementary modes of action, may halt or slow the progression of chronic hepatitis B virus, and may bring us closer to a functional cure of this devastating disease.”

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