Use of FDA approved therapeutics with hNTCP metabolic inhibitory properties to impair the HDV lifecycle.
Worldwide there are approximately 240million individuals chronically infected with the hepatitis B virus (HBV), including 15-20million coinfected with the hepatitis delta virus (HDV). Treatments available today are not fully efficient and often associated to important side effects and development of drug resistance. Targeting the HBV/HDV entry step using preS1-specific lipopeptides appears as a promising strategy to block viral entry for both HBV and HDV (Gripon et al., 2005; Petersen et al., 2008). Recently, the human Sodium Taurocholate Cotransporting Polypeptide (hNTCP) has been identified as a functional, preS1-specific receptor for HBV and HDV. This groundbreaking discovery has opened a very promising avenue for the treatment of chronic HBV and HDV infections. Here we investigated the ability of FDA approved therapeutics with documented inhibitory effect on hNTCP cellular function to impair viral entry using a HDV in vitro infection model based on a hNTCP-expressing Huh7 cell line. We demonstrate the potential of three FDA approved molecules, irbesartan, ezetimibe, and ritonavir, to alter HDV infection in vitro.
INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Canada.
Matthieu
M
Blanchet
Institut National de la Transfusion Sanguine, Paris, France.
Camille
C
Sureau
INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Canada. Electronic address: patrick.labonte@iaf.inrs.ca.
Patrick
P
Labonté
D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001384:Azetidines / Q000302:isolation & purification / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D000069438:Ezetimibe; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D003698:Hepatitis Delta Virus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D000077405:Irbesartan; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors*; D019438:Ritonavir / Q000302:isolation & purification / Q000494:pharmacology; D027981:Symporters / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000302:isolation & purification / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects*
D000998:Antiviral Agents; D001384:Azetidines; D001713:Biphenyl Compounds; D029363:Organic Anion Transporters, Sodium-Dependent; D011991:Receptors, Virus; D027981:Symporters; D013777:Tetrazoles; C071908:sodium-bile acid cotransporter; D000069438:Ezetimibe; D000077405:Irbesartan; D019438:Ritonavir
Antivirals; FDA approved therapeutics; Hepatitis B virus; Hepatitis delta virus; Infection; hNTCP