1. Academic Validation
  2. Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion

Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion

  • Virol Sin. 2021 Jun;36(3):501-509. doi: 10.1007/s12250-020-00306-2.
Jing Li 1 2 Yangyang Hu 2 3 Yifei Yuan 2 Yinan Zhao 1 2 Qiqi Han 1 Canyu Liu 2 Xue Hu 2 Yuan Zhou 2 Yun Wang 2 Yu Guo 1 Chunchen Wu 2 4 Xinwen Chen 5 6 Rongjuan Pei 7
Affiliations

Affiliations

  • 1 College of Pharmacy, Nankai University, Tianjin, 300350, China.
  • 2 State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
  • 3 Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
  • 4 Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Wuhan, 430070, China.
  • 5 State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. chenxw@wh.iov.cn.
  • 6 Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. chenxw@wh.iov.cn.
  • 7 State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China. rongjuan_pei@wh.iov.cn.
Abstract

Hepatitis B virus (HBV) belongs to Hepadnaviridae family and mainly infects hepatocytes, which can cause acute or chronic hepatitis. Currently, two types of Antiviral drugs are approved for chronic Infection clinically: interferons and nucleos(t)ide analogues. However, the clinical cure for chronic Infection is still rare, and it is a huge challenge for all researchers to develop high-efficiency, safe, non-tolerant, and low-toxicity anti-HBV drugs. Antazoline hydrochloride is a first-generation antihistamine with anticholinergic properties, and it is commonly used to relieve nasal congestion and in eye drops. Recently, an in vitro high-throughput evaluation system was constructed to screen nearly 800 compounds from the Food and Drug Administration (FDA)-approved Drug Library. We found that arbidol hydrochloride and antazoline hydrochloride can effectively reduce HBV DNA in the extracellular supernatant in a dose-dependent manner, with EC50 of 4.321 μmol/L and 2.910 μmol/L in HepAD38 cells, respectively. Moreover, the Antiviral effects and potential mechanism of action of antazoline hydrochloride were studied in different HBV replication systems. The results indicate that antazoline hydrochloride also has a significant inhibitory effect on HBV DNA in the extracellular supernatant of Huh7 cells, with an EC50 of 2.349 μmol/L. These findings provide new ideas for screening and research related to HBV agents.

Keywords

Antazoline hydrochloride; HepAD38; Hepatitis B virus (HBV); High-throughput evaluation system.

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