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Antimicrobial Agents and Chemotherapy, June 2004, p. 2085-2090, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2085-2090.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

{alpha}-Galactosylceramide and Novel Synthetic Glycolipids Directly Induce the Innate Host Defense Pathway and Have Direct Activity against Hepatitis B and C Viruses

Anand S. Mehta,1* Baohua Gu,1 Bertha Conyers,1 Serguey Ouzounov,1 Lijuan Wang,1 Robert M. Moriarty,2 Raymond A. Dwek,3 and Timothy M. Block1

Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, The Jefferson Center, Doylestown, Pennsylvania 18901,1 Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607,2 Department of Biochemistry, The Glycobiology Institute, University of Oxford, Oxford, United Kingdom OX1 3QU3

Received 17 September 2003/ Returned for modification 16 December 2003/ Accepted 20 February 2004

{alpha}-Galactosylceramide is a glycolipid derived from marine sponges that is currently in human clinical trials as an anticancer agent. It has also been shown to be effective in reducing the amount of hepatitis B virus (HBV) DNA detected in mice that produce HBV constitutively from a transgene. It was assumed that all of the antiviral and antitumor activities associated with {alpha}-galactosylceramide were mediated through the activation of NK T cells. However, we report here an additional unpredicted activity of {alpha}-galactosylceramide as a direct antiviral agent and inducer of the innate host defense pathway. To exploit this activity, we have developed a new class of smaller, orally available glycolipids that also induce the innate host defense pathway and have direct activity against HBV and hepatitis C virus.

* Corresponding author. Mailing address: Department of Biochemistry, The Jefferson Center, Jefferson Medical College, 700 E. Butler Ave., Doylestown, PA 18901. Phone: (215) 489-4905. Fax: (215) 489-4920. E-mail: anand.mehta{at}jefferson.edu.

Antimicrobial Agents and Chemotherapy, June 2004, p. 2085-2090, Vol. 48, No. 6
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.6.2085-2090.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Dougherty, A. M., Guo, H., Westby, G., Liu, Y., Simsek, E., Guo, J.-T., Mehta, A., Norton, P., Gu, B., Block, T., Cuconati, A. (2007). A Substituted Tetrahydro-Tetrazolo-Pyrimidine Is a Specific and Novel Inhibitor of Hepatitis B Virus Surface Antigen Secretion. Antimicrob. Agents Chemother. 51: 4427-4437 [Abstract] [Full Text]  


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