Background: Little is known about the early steps of the HBV life cycle due to the lack of susceptible cells permissive for viral infection. Hence, viral entry has not been exploited for antiviral targets, but the recent seminal discovery of sodium taurocholate co-transporting polypeptide (NTCP) as the cellular receptor for HBV entry opened up many avenues of investigation, making HBV entry amenable to therapeutic intervention. Methods: In order to exploit HBV entry, we established a HepG2-NTCP cell line that supports HBV infection. Over 70% of cells were infected at a dose of 104 genome equivalents (GEq) per cell. Several FDA-approved drugs with NTCP-inhibiting activity were tested for their ability to inhibit HBV infection of the cell line. Results: Consistent with their NTCP inhibitory activities, our results showed that several of them inhibit HBV infection. In particular, irbesartan, a drug used for the treatment of hypertension, inhibits HBV infection at the 50% effective concentration value of 35 μM. Conclusions: The observation that the pharmacological inhibitors of the NTCP transporter could block HBV entry suggests that NTCP represents an attractive molecular target for therapeutic intervention in HBV infection.
Bibliographical noteFunding Information:
This work was supported, in part, by the following National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP): NRF-2012R1A2A2A01007811 and NRF-2014R1A2A1A11052535. CK was supported by NRF Grant funded by the Korean Government: NRF-2011-Fostering Core Leaders of the Future Basic Science Program.
©2015 International Medical Press.
All Science Journal Classification (ASJC) codes
- Pharmacology (medical)
- Infectious Diseases