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

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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 anta-zoline 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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