This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ASM journals
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bryant, M. L.
Right arrow Articles by Sommadossi, J.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bryant, M. L.
Right arrow Articles by Sommadossi, J.-P.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2001, p. 229-235, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.229-235.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antiviral L-Nucleosides Specific for Hepatitis B Virus Infection

Martin L. Bryant,1,* Edward G. Bridges,1 Laurent Placidi,2 Abdesslem Faraj,2 Anna-Giulia Loi,3 Claire Pierra,3 David Dukhan,3 Gilles Gosselin,4 Jean-Louis Imbach,4 Brenda Hernandez,2 Amy Juodawlkis,1 Bud Tennant,5 Brent Korba,6 Paul Cote,6 Pat Marion,7 Erika Cretton-Scott,2 Raymond F. Schinazi,8 and Jean-Pierre Sommadossi2

Novirio Pharmaceuticals, Inc., Cambridge, Massachusetts 021401; Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, The Liver Center, University of Alabama at Birmingham, Birmingham, Alabama 352942; Novirio Pharmaceuticals, SARL, 75008 Paris,3 and Laboratoire de Chimie Bioorganique, CNRS UMR 5625, Université de Montpellier II, 34095 Cedex 5 Montpellier,4 France; Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 148535; Division of Molecular Virology and Immunology, Georgetown University College of Medicine, Rockville, Maryland 208526; Divisions of Gastroenterology and Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California 943057; and Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, Georgia 300338

Received 10 April 2000/Returned for modification 20 June 2000/Accepted 10 October 2000

A unique series of simple "unnatural" nucleosides has been discovered to inhibit hepatitis B virus (HBV) replication. Through structure-activity analysis it was found that the 3'-OH group of the beta -L-2'-deoxyribose of the beta -L-2'-deoxynucleoside confers specific antihepadnavirus activity. The unsubstituted nucleosides beta -L-2'-deoxycytidine, beta -L-thymidine, and beta -L-2'-deoxyadenosine had the most potent, selective, and specific antiviral activity against HBV replication. Human DNA polymerases (alpha , beta , and gamma ) and mitochondrial function were not affected. In the woodchuck model of chronic HBV infection, viral load was reduced by as much as 108 genome equivalents/ml of serum and there was no drug-related toxicity. In addition, the decline in woodchuck hepatitis virus surface antigen paralleled the decrease in viral load. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.

* Corresponding author. Mailing address: Novirio Pharmaceuticals, Inc., 125 Cambridge Park Dr., Cambridge, MA 02140. Phone: (617) 250-3100. Fax: (617) 250-3101. E-mail: bryant.martin{at}novirio.com.

Antimicrobial Agents and Chemotherapy, January 2001, p. 229-235, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.229-235.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Poordad, F., Zeldin, G., Harris, S. I., Ke, J., Xu, L., Mayers, D., Zhou, X.-J. (2009). Absence of Effect of Telbivudine on Cardiac Repolarization: Results of a Thorough QT/QTc Study in Healthy Participants. J Clin Pharmacol 49: 1436-1446 [Abstract] [Full Text]  
  • Michalak, T. I., Zhang, H., Churchill, N. D., Larsson, T., Johansson, N.-G., Oberg, B. (2009). Profound Antiviral Effect of Oral Administration of MIV-210 on Chronic Hepadnaviral Infection in a Woodchuck Model of Hepatitis B. Antimicrob. Agents Chemother. 53: 3803-3814 [Abstract] [Full Text]  
  • Zhou, X.-J., Ke, J., Sallas, W. M., Farrell, C., Mayers, D. L., Pentikis, H. S. (2009). Population Pharmacokinetics of Telbivudine and Determination of Dose Adjustment for Patients With Renal Impairment. J Clin Pharmacol 49: 725-734 [Abstract] [Full Text]  
  • Bridges, E. G., Selden, J. R., Luo, S. (2008). Nonclinical Safety Profile of Telbivudine, a Novel Potent Antiviral Agent for Treatment of Hepatitis B. Antimicrob. Agents Chemother. 52: 2521-2528 [Abstract] [Full Text]  
  • Menne, S., Asif, G., Narayanasamy, J., Butler, S. D., George, A. L., Hurwitz, S. J., Schinazi, R. F., Chu, C. K., Cote, P. J., Gerin, J. L., Tennant, B. C. (2007). Antiviral Effect of Orally Administered ( )-{beta}-D-2-Aminopurine Dioxolane in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrob. Agents Chemother. 51: 3177-3184 [Abstract] [Full Text]  
  • Alexandre, J. A.C., Roy, B., Topalis, D., Pochet, S., Perigaud, C., Deville-Bonne, D. (2007). Enantioselectivity of human AMP, dTMP and UMP-CMP kinases. Nucleic Acids Res 0: gkm479v1-10 [Abstract] [Full Text]  
  • Matthes, E., Funk, A., Krahn, I., Gaertner, K., von Janta-Lipinski, M., Lin, L., Will, H., Sirma, H. (2007). Strong and Selective Inhibitors of Hepatitis B Virus Replication among Novel N4-Hydroxy- and 5-Methyl-{beta}-L-Deoxycytidine Analogues. Antimicrob. Agents Chemother. 51: 2523-2530 [Abstract] [Full Text]  
  • Hu, P., Jiang, J., Wang, H., Pietropaolo, K., Chao, G. C., Brown, N. A., Zhou, X.-J. (2006). Single-dose and multiple-dose pharmacokinetics and safety of telbivudine after oral administration in healthy chinese subjects.. J Clin Pharmacol 46: 999-1007 [Abstract] [Full Text]  
  • Zhou, X.-J., Fielman, B. A., Lloyd, D. M., Chao, G. C., Brown, N. A. (2006). Pharmacokinetics of Telbivudine in Healthy Subjects and Absence of Drug Interaction with Lamivudine or Adefovir Dipivoxil. Antimicrob. Agents Chemother. 50: 2309-2315 [Abstract] [Full Text]  
  • Zhou, X.-J., Marbury, T. C., Alcorn, H. W., Smith, W. B., Dubuc Patrick, G., Chao, G. C., Brown, N. A. (2006). Pharmacokinetics of Telbivudine in Subjects with Various Degrees of Hepatic Impairment. Antimicrob. Agents Chemother. 50: 1721-1726 [Abstract] [Full Text]  
  • Zhou, X.-J., Lim, S.-G., Lloyd, D. M., Chao, G. C., Brown, N. A., Lai, C.-L. (2006). Pharmacokinetics of Telbivudine following Oral Administration of Escalating Single and Multiple Doses in Patients with Chronic Hepatitis B Virus Infection: Pharmacodynamic Implications. Antimicrob. Agents Chemother. 50: 874-879 [Abstract] [Full Text]  
  • Zhou, X.-J., Lloyd, D. M., Chao, G. C., Brown, N. A. (2006). Absence of food effect on the pharmacokinetics of telbivudine following oral administration in healthy subjects.. J Clin Pharmacol 46: 275-281 [Abstract] [Full Text]  
  • Kim, J. W, Park, S. H, Louie, S. G (2006). Telbivudine: A Novel Nucleoside Analog for Chronic Hepatitis B. The Annals of Pharmacotherapy 40: 472-478 [Abstract] [Full Text]  
  • Menne, S., Cote, P. J., Korba, B. E., Butler, S. D., George, A. L., Tochkov, I. A., Delaney, W. E. IV, Xiong, S., Gerin, J. L., Tennant, B. C. (2005). Antiviral Effect of Oral Administration of Tenofovir Disoproxil Fumarate in Woodchucks with Chronic Woodchuck Hepatitis Virus Infection. Antimicrob. Agents Chemother. 49: 2720-2728 [Abstract] [Full Text]  
  • Delaney, W. E. IV, Yang, H., Miller, M. D., Gibbs, C. S., Xiong, S. (2004). Combinations of Adefovir with Nucleoside Analogs Produce Additive Antiviral Effects against Hepatitis B Virus In Vitro. Antimicrob. Agents Chemother. 48: 3702-3710 [Abstract] [Full Text]  
  • Iyer, R. P., Jin, Y., Roland, A., Morrey, J. D., Mounir, S., Korba, B. (2004). Phosphorothioate Di- and Trinucleotides as a Novel Class of Anti-Hepatitis B Virus Agents. Antimicrob. Agents Chemother. 48: 2199-2205 [Abstract] [Full Text]  
  • Karayiannis, P. (2003). Hepatitis B virus: old, new and future approaches to antiviral treatment. J Antimicrob Chemother 51: 761-785 [Abstract] [Full Text]  
  • Yuen, M.-F., Lai, C.-L. (2003). Current and future antiviral agents for chronic hepatitis B. J Antimicrob Chemother 51: 481-485 [Full Text]  
  • Hernandez-Santiago, B., Placidi, L., Cretton-Scott, E., Faraj, A., Bridges, E. G., Bryant, M. L., Rodriguez-Orengo, J., Imbach, J. L., Gosselin, G., Pierra, C., Dukhan, D., Sommadossi, J. P. (2002). Pharmacology of {beta}-L-Thymidine and {beta}-L-2'-Deoxycytidine in HepG2 Cells and Primary Human Hepatocytes: Relevance to Chemotherapeutic Efficacy against Hepatitis B Virus. Antimicrob. Agents Chemother. 46: 1728-1733 [Abstract] [Full Text]  
  • Di Bisceglie, A M (2002). Combination therapy for hepatitis B. Gut 50: 443-445 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»