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Antimicrobial Agents and Chemotherapy, May 2007, p. 1780-1786, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01001-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Direct Inactivation of Human Immunodeficiency Virus Type 1 by a Novel Small-Molecule Entry Inhibitor, DCM205{triangledown}

Yen T. Duong,1 D. Christopher Meadows,1,2 Indresh K. Srivastava,3 Jacquelyn Gervay-Hague,2 and Thomas W. North1,4*

Center for Comparative Medicine, University of California, Davis, Davis, California 95616,1 Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616,2 Immunology and Cell Biology, Novartis Vaccines and Diagnostics (NOVAD), 4560 Horton Street, Emeryville, California 94608,3 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California 956164

Received 10 August 2006/ Returned for modification 9 November 2006/ Accepted 8 February 2007

With more than 40 million people living with human immunodeficiency virus (HIV), there is an urgent need to develop drugs that can be used in the form of a topical microbicide to prevent infection through sexual transmission. DCM205 is a recently discovered small-molecule inhibitor of HIV type 1 (HIV-1) that is able to directly inactivate HIV-1 in the absence of a cellular target. DCM205 is active against CXCR4-, CCR5-, and dual-tropic laboratory-adapted and primary strains of HIV-1. DCM205 binds to the HIV-1 envelope glycoprotein, and competition studies map the DCM205 binding at or near the V3 loop of gp120. Binding to this site interferes with the soluble CD4 interaction. With its ability to disable the virus particle, DCM205 represents a promising new class of HIV entry inhibitor that can be used as a strategy in the prevention of HIV-1/AIDS.

* Corresponding author. Mailing address: Center for Comparative Medicine, University of California, Davis, Davis, CA 95616. Phone: (530) 752-3414. Fax: (530) 752-7914. E-mail: twnorth{at}ucdavis.edu

{triangledown} Published ahead of print on 16 February 2007.

Antimicrobial Agents and Chemotherapy, May 2007, p. 1780-1786, Vol. 51, No. 5
0066-4804/07/$08.00+0     doi:10.1128/AAC.01001-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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