Aa
CRV431
EDISON, N.J., Dec. 8, 2016 /PRNewswire/ -- ContraVir Pharmaceuticals, Inc. (CTRV), a biopharmaceutical company focused on the development and commercialization of targeted antiviral therapies, today provided new insights into the mechanism of action of its hepatitis B (HBV)-optimized cyclophilin inhibitor CRV431, showing that it effectively blocks a critical interaction between HBV X protein (HBx) and host cyclophilin A, with nanomolar potency. CRV431 is believed to be the first antiviral drug with the potential to selectively block the HBx pathway, which is known to play several significant roles in HBV infection including protecting infected liver cells from immune destruction, and promoting the development of liver cancer.
HBx is a multifunctional viral protein known to be essential for HBV replication and for the maintenance and progression of chronic HBV disease. HBx is involved in the production and secretion of key viral proteins, such as HBsAg and HBeAg. HBx further disables host factors that restrict the production of HBV and other viral products, including covalently closed circular DNA (cccDNA) which is key to the persistence of chronic HBV infection. ContraVir's recent in vitro studies indicate that CRV431 blocks the interaction between HBx and cyclophilin A, which is required for HBx to function fully.
Importantly, HBx is required early in the viral life cycle and works "upstream" of other classes of anti-HBV drugs. CRV431 therefore could potentially interrupt several essential pathways enabling development of a curative combination with other HBV treatments. CRV431 has demonstrated synergistic activity in vitro with ContraVir's tenofovir prodrug CMX157, currently in Phase 2 clinical trials.
"Identifying this exciting mechanism of action for CRV431 places ContraVir at the very forefront of HBV research, with a compound that can effectively target the HBx pathway," said James Sapirstein, CEO of ContraVir. "Further development of this novel compound, and ultimately layering it on top of CMX157 and potentially other HBV drugs, dovetails with our overall development strategy which is focused on finding a functional cure for HBV. The pathogenic effects of HBx are many, and we would therefore expect the anti-HBx activity of CRV431 to be equally robust. We will continue to work on characterizing the activity of CRV431 and its impact on HBx and HBV within our company, and through our peers in North America and Europe."
Philippe Gallay, Ph.D., Professor at The Scripps Research Institute, who conducted the in vitro study, commented, "HBx and its involvement in the pathogenesis of HBV is widely supported by the scientific literature, and its importance as a high-value drug target was highlighted at the recent joint HBV conference hosted by the American Association of the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL). However, until now, we hadn't confirmed the ability of an antiviral drug to bind to a specific ligand of HBx – cyclophilin A. CRV431 may therefore be unique as a small molecule drug that selectively targets the function of HBx and thus has the potential to repress, among other things, cccDNA transcription, which has exciting implications about its potential to significantly inhibit HBV when used together with complementary antivirals. We are proud to lead this cutting edge research by continuing to advance CRV431."
HBx is a multifunctional viral protein known to be essential for HBV replication and for the maintenance and progression of chronic HBV disease. HBx is involved in the production and secretion of key viral proteins, such as HBsAg and HBeAg. HBx further disables host factors that restrict the production of HBV and other viral products, including covalently closed circular DNA (cccDNA) which is key to the persistence of chronic HBV infection. ContraVir's recent in vitro studies indicate that CRV431 blocks the interaction between HBx and cyclophilin A, which is required for HBx to function fully.
Importantly, HBx is required early in the viral life cycle and works "upstream" of other classes of anti-HBV drugs. CRV431 therefore could potentially interrupt several essential pathways enabling development of a curative combination with other HBV treatments. CRV431 has demonstrated synergistic activity in vitro with ContraVir's tenofovir prodrug CMX157, currently in Phase 2 clinical trials.
"Identifying this exciting mechanism of action for CRV431 places ContraVir at the very forefront of HBV research, with a compound that can effectively target the HBx pathway," said James Sapirstein, CEO of ContraVir. "Further development of this novel compound, and ultimately layering it on top of CMX157 and potentially other HBV drugs, dovetails with our overall development strategy which is focused on finding a functional cure for HBV. The pathogenic effects of HBx are many, and we would therefore expect the anti-HBx activity of CRV431 to be equally robust. We will continue to work on characterizing the activity of CRV431 and its impact on HBx and HBV within our company, and through our peers in North America and Europe."
Philippe Gallay, Ph.D., Professor at The Scripps Research Institute, who conducted the in vitro study, commented, "HBx and its involvement in the pathogenesis of HBV is widely supported by the scientific literature, and its importance as a high-value drug target was highlighted at the recent joint HBV conference hosted by the American Association of the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL). However, until now, we hadn't confirmed the ability of an antiviral drug to bind to a specific ligand of HBx – cyclophilin A. CRV431 may therefore be unique as a small molecule drug that selectively targets the function of HBx and thus has the potential to repress, among other things, cccDNA transcription, which has exciting implications about its potential to significantly inhibit HBV when used together with complementary antivirals. We are proud to lead this cutting edge research by continuing to advance CRV431."
Have an Answer?
You are reading content posted in the Hepatitis B Community
A list of national and international resources and hotlines to help connect you to needed health and medical services.
Herpes sores blister, then burst, scab and heal.
Herpes spreads by oral, vaginal and anal sex.
STIs are the most common cause of genital sores.
Condoms are the most effective way to prevent HIV and STDs.
PrEP is used by people with high risk to prevent HIV infection.
