Curcumin inhibited hepatitis B viral entry through NTCP binding

Piyanoot Thongsri,Khanit Sa-Ngiamsuntorn,Yongyut Pewkliang,Suradej Hongeng,Adisak Wongkajornsilp,Suparerk Borwornpinyo

doi:10.1038/s41598-021-98243-x

Piyanoot Thongsri, Khanit Sa-Ngiamsuntorn + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-98243-x

Copy DOI

Abstract

Hepatitis B virus (HBV) has been implicated in hepatitis and hepatocellular carcinoma. Current agents (nucleos(t)ide analogs and interferons) could only attenuate HBV infection. A combination of agents targeting different stages of viral life cycle (e.g., entry, replication, and cccDNA stability) was expected to eradicate the infection. Curcumin (CCM) was investigated for inhibitory action toward HBV attachment and internalization. Immortalized hepatocyte-like cells (imHCs), HepaRG and non-hepatic cells served as host cells for binding study with CCM. CCM decreased viral load, HBeAg, HBcAg (infectivity), intracellular HBV DNA, and cccDNA levels. The CCM-induced suppression of HBV entry was directly correlated with the density of sodium-taurocholate co-transporting polypeptide (NTCP), a known host receptor for HBV entry. The site of action of CCM was confirmed using TCA uptake assay. The affinity between CCM and NTCP was measured using isothermal titration calorimetry (ITC). These results demonstrated that CCM interrupted HBV entry and would therefore suppress HBV re-infection.

Highlights

Hepatitis B virus (HBV) has been implicated in hepatitis and hepatocellular carcinoma
HBV and HDV entered host cells through endocytosis mediated by sodium-taurocholate co-transporting polypeptide (NTCP) and enhanced by heparan sulfate proteoglycans (HSPGs)[4,5,6]
We investigated the inhibitory action of CCM toward NTCP-mediated HBV entry. Immortalized hepatocyte-like cells (imHCs) and others were used as host cells for HBV infection[22]

Summary

Introduction

Hepatitis B virus (HBV) has been implicated in hepatitis and hepatocellular carcinoma. The affinity between CCM and NTCP was measured using isothermal titration calorimetry (ITC) These results demonstrated that CCM interrupted HBV entry and would suppress HBV re-infection. HBV and HDV entered host cells through endocytosis mediated by sodium-taurocholate co-transporting polypeptide (NTCP) and enhanced by heparan sulfate proteoglycans (HSPGs)[4,5,6]. The pretreatment of host cells with heparin or cyclosporine A that targeted viral receptors could inhibit HBV infection. A few cultured cell models allowed HBV entry and replication These included primary human hepatocyte (PHH) and differentiated HepaRG (d-HepaRG)[15,16]. We investigated the inhibitory action of CCM toward NTCP-mediated HBV entry. CCM lessened HBV entry through NTCP binding. This resulted in decreasing all HBV viral makers in infected hepatocytes

Methods

Results

Conclusion