A Korean research team has found a new way to inhibit the growth of hepatitis C virus.
A research team led by Professor Kim Jong-heon of the National Cancer Center announced on the 4th that they have identified the key mechanism by which hepatitis C virus proliferates. A new drug candidate to treat hepatitis C was also found. The research team expected that this candidate material might be a new drug to replace Gilead Sciences’ hepatitis C treatment ‘Sovaldi (ingredient name: Sofosbuvir)’.
If hepatitis C, which is mainly transmitted through blood, leads to chronic hepatitis, it is very likely to develop into cirrhosis or liver cancer. There is no vaccine developed so far, and there are regarding 100 million hepatitis C patients worldwide.
The research team identified the upper signaling pathway PLK1 (polo-like protein kinase 1)-ELAVL1/HuR (human antigen R) mechanism that regulates microRNA-122 (miR-122), which plays a key role in virus proliferation.
miR-122 is a 22-sequence microRNA that is expressed only in the liver. MicroRNA, a small RNA fragment with 21 to 23 sequences, has a different function from existing RNA and mainly regulates protein expression by combining with mRNA. miR-122 binds to the 5 prime end of hepatitis C virus RNA, stabilizes the viral RNA and amplifies protein expression to help the virus multiply.
By identifying the signal transduction mechanism that regulates miR-122, the research team also discovered ‘Rigosertip’, an antiviral drug candidate that regulates miR-122. The research team explains that Rigosertip inhibits the proliferation of hepatitis C virus by inhibiting the kinase function of intracellular PLK1 and finally inhibiting the PLK1 sub-signaling process (ELAVL1/HuR-miR-122).
The research team confirmed the antiviral efficacy of Rigosertip through liver cancer cell lines and animal experiments, and is currently conducting phase 3 clinical trials as an anticancer drug candidate. The research team has completed a patent application for a luminescent sensor system that can sensitively detect hepatitis C virus proliferation and miR-122 regulation at the same time, and additional research for basic research, new drug development and discovery is also underway.
Professor Kim, the main corresponding author of the research paper, said, “Rigosertip, a new drug candidate discovered in relation to miR-122, is expected to be a new type of treatment candidate that inhibits the proliferation of hepatitis C virus, which is closely related to liver cancer in the future. “Rigosertip, discovered through this study, will be an alternative to overcome the RNA virus mutation resistance, which is the Achilles heel of the blockbuster drug ‘sofosbuvir’ developed by Gilead Sciences.” he emphasized.
Researcher Yuna Seo of the Department of Cancer Molecular Biology at the National Cancer Center, Park Jong-bae, Director of Industry-University Cooperation at the Graduate School of International Cancer Research, and Korea Research Institute of Bioscience and Biotechnology, Senior Researcher Cho Seong-chan participated in this study. done.
