Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion
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RESEARCH ARTICLE
Repurposing of Antazoline Hydrochloride as an Inhibitor of Hepatitis B Virus DNA Secretion Jing Li1,2 • Yangyang Hu2,3 • Yifei Yuan2 • Yinan Zhao1,2 • Qiqi Han1 • Canyu Liu2 • Xue Hu2 • Yuan Zhou2 Yun Wang2 • Yu Guo1 • Chunchen Wu2,5 • Xinwen Chen2,4 • Rongjuan Pei2
•
Received: 26 March 2020 / Accepted: 16 September 2020 Ó Wuhan Institute of Virology, CAS 2020
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 lmol/L and 2.910 lmol/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 lmol/L. These findings provide new ideas for screening and research related to HBV agents. Keywords Antazoline hydrochloride Hepatitis B virus (HBV) High-throughput evaluation system HepAD38
Introduction
Jing Li and Yangyang Hu have contributed equally to this work. & Rongjuan Pei [email protected] & Xinwen Chen [email protected] 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
Hepatitis B virus (HBV) belongs to the hepadnaviridae family and mainly infects hepatocytes, potentially causing acute or chronic hepatitis, cirrhosis and even hepatocellular carcinoma (HCC), and seriously threatening human health (Schweitzer et al. 2015). According to the World Health Organization (WHO) recently, approximately 240 million people worldwide suffer from chronic infections and approximately 680,000 people die from liver disease ca
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