The major cause of chronic liver disease is the Hepatitis C virus (HCV). HCV is able to establish a chronic infection that may lead to liver fibrosis, liver cirrhosis, and hepatocellular carcinoma
The genome of HCV is approximately 9.6 kb and has an open reading frame (ORF) which encodes a polyprotein precursor.
Viral and host proteases can cleave those polyprotein precursors into structural proteins, E1 and E2. At the same time, the cleaving of the non-structural (NS) proteins p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B3 is running in parallel.
The current standard treatment of HCV with Ribavirin is only effective in the most prevalent HCV subtypes. Furthermore, the side effects of Ribavirin, such as anemia, flu-like symptoms, fatigue also exist during the treatment.
In this article, we will introduce an HCV NS3/4A protease inhibitor, HZ-1157.
HZ-1157 inhibits HCV NS3/4A protease with an IC50 of 1.0 μM. It possesses a broad spectrum of biological activities, such as protein lysine methyltransferase G9a inhibition, SMN2 promoter activation, dihydrofolate reductase inhibition, and others.
This anti-HCV compound shows showed no specific inhibitory effect on HCV NS3/4A protease activity. Besides, HZ-1157 is an anti-dengue active compound as a 2,4-diaminoquinazoline derivative.
Dengue virus is a kind of RNA virus, both Dengue and HCV belong to the Flaviviridae family. They share a similar genome structure and life cycle, at the same time, both are positive-sense RNA viruses. The genome of DENV is 10.7 kb, which has 4 serotypes, DENV-1–DENV-4. DENV is the main cause of dengue fever, an infectious tropical disease.
Drugs or vaccines are not available to combat dengue viral infections now. as a result, it is important to uncover small molecules that have potent anti-dengue bioactivities.
HZ-1157 has a high dengue virus inhibitory activity (EC50 = 0.15 μM) and is a relatively nontoxic (CC50 > 10 μM) dengue antiviral agent.
In conclusion, HZ-1157 is an anti-HCV compound toward HCV NS3/4A protease. It also a novel and potent dengue virus inhibitor.
Reference:
[1]. Ye Yu, et al. Acta Pharmacol Sin. 2014 Aug;35(8):1074-81.
[2]. Bo Chao, et al. 2012 Apr 12;55(7):3135-43.