Citation: Jing Li, Yangyang Hu, Yifei Yuan, Yinan Zhao, Qiqi Han, Canyu Liu, Xue Hu, Yuan Zhou, Yun Wang, Yu Guo, Chunchen Wu, Xinwen Chen, Rongjuan Pei. Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion .VIROLOGICA SINICA, 2021, 36(3) : 501-509.  http://dx.doi.org/10.1007/s12250-020-00306-2

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

  • Corresponding author: Xinwen Chen, chenxw@wh.iov.cn, ORCID: http://orcid.org/0000-0002-40528155
    Rongjuan Pei, rongjuan_pei@wh.iov.cn, ORCID: http://orcid.org/0000-0002-5122-2944
  • Received Date: 26 March 2020
    Accepted Date: 16 September 2020
    Published Date: 09 November 2020
    Available online: 01 June 2021
  • 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.


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

      Corresponding author: Xinwen Chen, chenxw@wh.iov.cn
      Corresponding author: Rongjuan Pei, rongjuan_pei@wh.iov.cn
    • 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. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
    • 5. Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Wuhan 430070, China

    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.