Sodium taurocholate cotransporting polypeptide in HBV-related diseases: from underlying mechanisms to targeted therapies

Qiang Xie; Qingbo Liu; Xin Zheng; Leilei Fu; Hussein H Aly; Bo Liu

doi:10.1016/j.drudis.2026.104664

Sodium taurocholate cotransporting polypeptide in HBV-related diseases: from underlying mechanisms to targeted therapies

Drug Discov Today. 2026 Apr 7;31(3):104664. doi: 10.1016/j.drudis.2026.104664. Online ahead of print.

Authors

Qiang Xie¹, Qingbo Liu², Xin Zheng³, Leilei Fu⁴, Hussein H Aly⁵, Bo Liu⁶

Affiliations

¹ School of Preclinical Medicine and School of Nursing, Chengdu University, Chengdu 610100, China.
² Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
³ Department of Virology II, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Research Center for Biosafety, Laboratory Animal and Pathogen Bank, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
⁴ Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China. Electronic address: liubo2400@163.com.
⁵ Department of Virology II, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. Electronic address: hussein.a@jihs.go.jp.
⁶ Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address: leilei_fu@163.com.

PMID: 41956319
DOI: 10.1016/j.drudis.2026.104664

Abstract

Hepatitis B virus (HBV) remains a leading cause of liver fibrosis and hepatocellular carcinoma, posing a major global health burden. Current therapies, including interferons and nucleotide analogs, have limited curative efficacy. The identification of sodium taurocholate cotransporting polypeptide (NTCP) as the functional HBV entry receptor in 2012 was a pivotal advance, spurring intensive development of NTCP‑targeted entry inhibitors, although only two macromolecular candidates have progressed toward clinical application. In this review, we comprehensively summarize NTCP structure and function in HBV‑related liver disease and critically evaluate current NTCP‑directed antiviral strategies, with the aim of informing the rational design of next‑generation therapeutics.

Keywords: HBV; HCC; NTCP; NTCP inhibitor; Sodium taurocholate cotransporting polypeptide; endocytosis; hepatitis B virus; hepatocellular carcinoma.

Publication types

Review