Oleanolic Acid Derivative AXX-18 Exerts Antiviral Activity by Inhibiting the Expression of HSV-1 Viral Genes UL8 and UL52

Autor: Zhaoyang Wang, Jiaoyan Jia, Yuzhou Jiang, Feng Li, Yiliang Wang, Xiaowei Song, Shurong Qin, Yifei Wang, Kai Zheng, Binyuan Hu, Yongxian Cheng, Zhe Ren
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Viruses, Vol 14, Iss 6, p 1287 (2022)
Druh dokumentu: article
ISSN: 14061287
1999-4915
DOI: 10.3390/v14061287
Popis: 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.
Databáze: Directory of Open Access Journals
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