Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection

Tianhao Shan; Ju Ye; Jiaoyan Jia; Zhaoyang Wang; Yuzhou Jiang; Yiliang Wang; Yifei Wang; Kai Zheng; Zhe Ren

doi:10.3389/fmicb.2021.689607

Viral UL8 Is Involved in the Antiviral Activity of Oleanolic Acid Against HSV-1 Infection

Front Microbiol. 2021 Jul 20:12:689607. doi: 10.3389/fmicb.2021.689607. eCollection 2021.

Authors

Tianhao Shan^{1

2

3

4

5

6}, Ju Ye⁷, Jiaoyan Jia^{1

2

3

4

5

6}, Zhaoyang Wang^{1

2

3

4

5

6}, Yuzhou Jiang^{1

2

3

4

5

6}, Yiliang Wang^{1

2

3

4

5

6}, Yifei Wang^{1

2

3

4

5

6}, Kai Zheng⁸, Zhe Ren^{1

2

3

4

5

6}

Affiliations

¹ Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
² Key Laboratory of Virology of Guangzhou, Jinan University, Guangzhou, China.
³ Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, Guangzhou, China.
⁴ Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, China.
⁵ Guangdong Provincial Biotechnology Drug and Engineering Technology Research Center, Guangzhou, China.
⁶ National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
⁷ Key Laboratory of Plant Chemistry in Qinghai-Tibet Plateau, Qinghai University for Nationalities, Xining, China.
⁸ School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, China.

Abstract

Herpes simplex virus type 1 (HSV-1) is highly prevalent in humans and can cause severe diseases, especially in immunocompromised adults and newborns, such as keratitis and herpes simplex encephalitis. At present, the clinical therapeutic drug against HSV-1 infection is acyclovir (ACV), and its extensive usage has led to the emergence of ACV-resistant strains. Therefore, it is urgent to explore novel therapeutic targets and anti-HSV-1 drugs. This study demonstrated that Oleanolic acid, a pentacyclic triterpenoid widely existing in natural product, had strong antiviral activity against both ACV-sensitive and -resistant HSV-1 strains in different cells. Mechanism studies showed that Oleanolic acid exerted its anti-HSV-1 activity in the immediate early stage of infection, which involved the dysregulation of viral UL8, a component of viral helicase-primase complex critical for viral replication. In addition, Oleanolic acid significantly ameliorated the skin lesions in an HSV-1 infection mediated zosteriform model. Together, our study suggested that Oleanolic acid could be a potential candidate for clinical therapy of HSV-1 infection-related diseases.

Keywords: Oleanolic acid; UL8; helicase-primase complex; herpes simplex virus type 1; zosteriform model.