Oleanolic Acid Derivative AXX-18 Exerts Antiviral Activity by Inhibiting the Expression of HSV-1 Viral Genes UL8 and UL52
Zhaoyang Wang,
Jiaoyan Jia,
Yuzhou Jiang,
Feng Li,
Yiliang Wang,
Xiaowei Song,
Shurong Qin,
Yifei Wang,
Kai Zheng,
Binyuan Hu,
Yongxian Cheng,
Zhe Ren
Affiliations
Zhaoyang Wang
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Jiaoyan Jia
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Yuzhou Jiang
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Feng Li
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Yiliang Wang
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Xiaowei Song
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Shurong Qin
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Yifei Wang
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Kai Zheng
Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China
Binyuan Hu
Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China
Yongxian Cheng
Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China
Zhe Ren
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Two-thirds of the world’s population is infected with HSV-1, which is closely associated with many diseases, such as Gingival stomatitis and viral encephalitis. However, the drugs that are currently clinically effective in treating HSV-1 are Acyclovir (ACV), Ganciclovir, and Valacyclovir. Due to the widespread use of ACV, the number of drug-resistant strains of ACV is increasing, so searching for new anti-HSV-1 drugs is urgent. The oleanolic-acid derivative AXX-18 showed a CC50 value of 44.69 μM for toxicity to HaCaT cells and an EC50 value of 1.47 μM for anti-HSV-1/F. In addition, AXX-18 showed significant inhibition of ACV-resistant strains 153, 106, and Blue, and the anti-HSV-1 activity of AXX-18 was higher than that of oleanolic acid. The mechanism of action of AXX-18 was found to be similar to that of oleanolic acid, except that AXX-18 could act on both the UL8 and UL52 proteins of the uncoupling helicase-primase enzyme, whereas oleanolic acid could only act on the UL8 protein. We have elucidated the antiviral mechanism of AXX-18 in detail and, finally, found that AXX-18 significantly inhibited the formation of skin herpes. In conclusion, we have explored the anti-HSV-1 activity of AXX-18 in vitro and in vivo as well as identification of its potential target proteins, which will provide a theoretical basis for the development of subsequent anti-HSV-1 drugs.
