Potential for hepatitis C virus resistance to nitazoxanide or tizoxanide.

Antimicrobial Agents and Chemotherapy
Brent KorbaJeffrey S Glenn

Abstract

Nitazoxanide and its primary metabolite, tizoxanide, inhibit hepatitis C virus (HCV) replication in HCV replicon systems. To study the potential for resistance, we subjected Huh7 cells harboring HCV replicons to serial passage in 250 muM G418 and increasing concentrations of nitazoxanide or tizoxanide. Passage of the replicon-containing cell lines in either compound resulted in increases in the 50% effective concentrations (EC(50)s) (7- to 13-fold), EC(90)s (14- to 36-fold), and 50% cytotoxic concentrations (2- to 4-fold) of both compounds. Serial passage in either compound did not alter the susceptibility of HCV replicons to ribavirin or 2'-C-methylcytidine. Interestingly, serial passage in nitazoxanide or tizoxanide resulted in increased sensitivity to alpha interferon 2b: EC(50)s and EC(90)s were reduced three- and eightfold, respectively. Replicons isolated from these cell lines had no greater ability to confer tizoxanide resistance, or increased susceptibility to alpha interferon, than replicons isolated from the parental cell line that had not previously been exposed to nitazoxanide or tizoxanide. These findings are indicative of a cell-mediated activity differing from that of other anti-HCV drugs but complementary with i...Continue Reading

References

Apr 30, 2003·Journal of Virology·Menashe ElazarJeffrey S Glenn
Mar 26, 2005·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·LeAnne M Fox, Louis D Saravolatz
Oct 27, 2005·Nucleosides, Nucleotides & Nucleic Acids·C PierraG Gosselin
Nov 4, 2006·Alimentary Pharmacology & Therapeutics·J-F Rossignol, Y M El-Gohary

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Citations

Jun 22, 2010·Current HIV/AIDS Reports·Valerianna K Amorosa
May 11, 2011·Journal of Medicinal Chemistry·Andrew V StachulskiJean-Francois Rossignol
Nov 9, 2011·Journal of Medicinal Chemistry·Andrew V StachulskiJean-Francois Rossignol
May 17, 2012·Acta Crystallographica. Section E, Structure Reports Online·Huaqin ZhengDing Li
Mar 20, 2013·Antimicrobial Agents and Chemotherapy·Kristina ShigyoDaniel W Fitzgerald
Jun 28, 2011·Genetic Vaccines and Therapy·Sidra RehmanTariq Javed
Jul 10, 2010·Drugs·David A BoltzElena A Govorkova
Apr 17, 2009·World Journal of Gastroenterology : WJG·Emmet B Keeffe, Jean-François Rossignol
Jul 25, 2009·World Journal of Gastroenterology : WJG·Mahmoud Aboelneen Khattab
Sep 18, 2010·Veterinary Medicine International·Laura V AshtonGabriele A Landolt
May 21, 2009·Journal of Gastroenterology·Naoya Sakamoto, Mamoru Watanabe
Dec 18, 2012·Expert Review of Anti-infective Therapy·Aeron C HurtIan G Barr
Sep 13, 2011·Expert Review of Anti-infective Therapy·Maria Ripoli, Valerio Pazienza
May 16, 2009·Expert Opinion on Drug Metabolism & Toxicology·Jean-François Rossignol
Aug 27, 2011·Clinics in Liver Disease·Joseph Ahn, Steven L Flamm
Dec 17, 2009·Gastroenterology·Christoph Sarrazin, Stefan Zeuzem
Dec 12, 2012·Hepatology Research : the Official Journal of the Japan Society of Hepatology·P Patrick BasuRobert S Brown
Jul 31, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Hany M ShehabDalia M Deraz
Aug 12, 2014·Antiviral Research·Jean-François Rossignol
Oct 7, 2010·The Korean Journal of Hepatology·Jae Young Jang, Raymond T Chung
Nov 19, 2011·ACS Medicinal Chemistry Letters·Luiz Pedro S de CarvalhoCarl Nathan
Feb 2, 2017·Influenza and Other Respiratory Viruses·Paulina KoszalkaAeron C Hurt
Apr 10, 2018·Future Medicinal Chemistry·Andrew V StachulskiJean-Francois Rossignol
Sep 25, 2008·Future Microbiology·Jean-François Rossignol, Emmet B Keeffe
May 19, 2018·Viruses·Latavia SinghViness Pillay
Oct 22, 2020·British Journal of Clinical Pharmacology·Rajith K R RajoliAndrew Owen
Jan 6, 2010·Journal of Clinical Gastroenterology·Jean-Francois RossignolEmmet B Keeffe
Feb 19, 2021·Journal of Biomolecular Structure & Dynamics·Mona MosayebniaFarzad Kobarfard
Dec 23, 2020·ACS Infectious Diseases·Andrew V StachulskiPaul M O'Neill
Aug 27, 2019·ACS Infectious Diseases·Ryan O'HanlonMegan L Shaw
Mar 4, 2020·ACS Infectious Diseases·Jimin XuJia Zhou
Oct 27, 2021·Clinical Pharmacology and Therapeutics·Lauren E WalkerUNKNOWN AGILE platform

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