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Virus Res. 2019 Apr 2;263:102-111. doi: 10.1016/j.virusres.2019.01.004. Epub 2019 Jan 9.

Cetylpyridinium chloride interaction with the hepatitis B virus core protein inhibits capsid assembly.

Author information

1
Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-747, South Korea.
2
Department of Internal Medicine, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, 06125, South Korea.
3
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea.
4
Department of Biological Sciences, College of Natural Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-747, South Korea. Electronic address: drjung@snu.ac.kr.

Abstract

Hepatitis B virus (HBV) infection is a major risk factor for chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. While multiple hepatitis B drugs have been developed, build up of drug resistance during treatment or weak efficacies observed in some cases have limited their application. Therefore, there is an urgent need to develop substitutional pharmacological agents for HBV-infected individuals. Here, we identified cetylpyridinium chloride (CPC) as a novel inhibitor of HBV. Using computational docking of CPC to core protein, microscale thermophoresis analysis of CPC binding to viral nucleocapsids, and in vitro nucleocapsid formation assays, we found that CPC interacts with dimeric viral nucleocapsid protein (known as core protein or HBcAg) specifically. Compared with other HBV inhibitors, such as benzenesulfonamide (BS) and sulfanilamide (SA), CPC achieved significantly better reduction of HBV particle number in HepG2.2.15 cell line, a derivative of human HCC cells that stably expresses HBV. CPC also inhibited HBV replication in mouse hydrodynamic model system. Taken together, our results show that CPC inhibits capsid assembly and leads to reduced HBV biogenesis. Thus, CPC is an effective pharmacological agent that can reduce HBV particles.

KEYWORDS:

Antiviral; Capsid assembly inhibitor; Cetylpyridinium chloride (CPC); Drug synergism; Hepatitis B virus (HBV)

PMID:
30639191
DOI:
10.1016/j.virusres.2019.01.004
[Indexed for MEDLINE]

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