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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 \u03bcM for toxicity to HaCaT cells and an EC50 value of 1.47 \u03bcM 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.<\/jats:p>","DOI":"10.3390\/v14061287","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T01:43:32Z","timestamp":1655171012000},"page":"1287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oleanolic Acid Derivative AXX-18 Exerts Antiviral Activity by Inhibiting the Expression of HSV-1 Viral Genes UL8 and UL52"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhaoyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"},{"name":"Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, 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