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
Services
Right arrow Similar articles in this journal
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 Balzarini, J.
Right arrow Articles by Schols, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Balzarini, J.
Right arrow Articles by Schols, D.

 Previous Article  |  Next Article 

Journal of Virology, January 2007, p. 362-373, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01404-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pradimicin A, a Carbohydrate-Binding Nonpeptidic Lead Compound for Treatment of Infections with Viruses with Highly Glycosylated Envelopes, Such as Human Immunodeficiency Virus{triangledown}

Jan Balzarini,1* Kristel Van Laethem,1 Dirk Daelemans,1 Sigrid Hatse,1 Antonella Bugatti,2 Marco Rusnati,2 Yasuhiro Igarashi,3 Toshikazu Oki,4 and Dominique Schols1

Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium,1 Department of Biomedical Sciences and Biotechnology, University of Brescia, I-25123 Brescia, Italy,2 Biotechnology Research Center, Toyama Prefectural University, Kurokawa 5180, Kosugi, Imizu-shi, Toyama 939-0398, Japan,3 Keck School of Medicine, University of Southern California, Los Angeles, California4

Received 5 July 2006/ Accepted 6 October 2006

Pradimicin A (PRM-A), an antifungal nonpeptidic benzonaphtacenequinone antibiotic, is a low-molecular-weight (molecular weight, 838) carbohydrate binding agent (CBA) endowed with a selective inhibitory activity against human immunodeficiency virus (HIV). It invariably inhibits representative virus strains of a variety of HIV-1 clades with X4 and R5 tropisms at nontoxic concentrations. Time-of-addition studies revealed that PRM-A acts as a true virus entry inhibitor. PRM-A specifically interacts with HIV-1 gp120 and efficiently prevents virus transmission in cocultures of HUT-78/HIV-1 and Sup T1 cells. Upon prolonged exposure of HIV-1-infected CEM cell cultures, PRM-A drug pressure selects for mutant HIV-1 strains containing N-glycosylation site deletions in gp120 but not gp41. A relatively long exposure time to PRM-A is required before drug-resistant virus strains emerge. PRM-A has a high genetic barrier, since more than five N-glycosylation site deletions in gp120 are required to afford moderate drug resistance. Such mutated virus strains keep full sensitivity to the other known clinically used anti-HIV drugs. PRM-A represents the first prototype compound of a nonpeptidic CBA lead and, together with peptide-based lectins, belongs to a conceptually novel type of potential therapeutics for which drug pressure results in the selection of glycan deletions in the HIV gp120 envelope.

* Corresponding author. Mailing address: Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32-16-337352. Fax: 32-16-337340. E-mail: jan.balzarini{at}rega.kuleuven.ac.be.

{triangledown} Published ahead of print on 18 October 2006.

Journal of Virology, January 2007, p. 362-373, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01404-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Francois, K. O., Pannecouque, C., Auwerx, J., Lozano, V., Perez-Perez, M.-J., Schols, D., Balzarini, J. (2009). The Phthalocyanine Prototype Derivative Alcian Blue Is the First Synthetic Agent with Selective Anti-Human Immunodeficiency Virus Activity Due to Its gp120 Glycan-Binding Potential. Antimicrob. Agents Chemother. 53: 4852-4859 [Abstract] [Full Text]  
  • Vermeire, K., Van Laethem, K., Janssens, W., Bell, T. W., Schols, D. (2009). Human Immunodeficiency Virus Type 1 Escape from Cyclotriazadisulfonamide-Induced CD4-Targeted Entry Inhibition Is Associated with Increased Neutralizing Antibody Susceptibility. J. Virol. 83: 9577-9583 [Abstract] [Full Text]  
  • Balestrieri, E., Ascolani, A., Igarashi, Y., Oki, T., Mastino, A., Balzarini, J., Macchi, B. (2008). Inhibition of Cell-to-Cell Transmission of Human T-Cell Lymphotropic Virus Type 1 In Vitro by Carbohydrate-Binding Agents. Antimicrob. Agents Chemother. 52: 2771-2779 [Abstract] [Full Text]  
  • Francois, K. O., Auwerx, J., Schols, D., Balzarini, J. (2008). Simian Immunodeficiency Virus Is Susceptible to Inhibition by Carbohydrate-Binding Agents in a Manner Similar to That of HIV: Implications for Further Preclinical Drug Development. Mol. Pharmacol. 74: 330-337 [Abstract] [Full Text]  
  • van der Meer, F. J. U. M., de Haan, C. A. M., Schuurman, N. M. P., Haijema, B. J., Verheije, M. H., Bosch, B. J., Balzarini, J., Egberink, H. F. (2007). The carbohydrate-binding plant lectins and the non-peptidic antibiotic pradimicin A target the glycans of the coronavirus envelope glycoproteins. J Antimicrob Chemother 60: 741-749 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»