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Journal of Virology, September 2009, p. 9175-9182, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00820-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Nucleocapsid Inhibitors Impede trans Infection in Cellular and Explant Models and Protect Nonhuman Primates from Infection {triangledown} ,§

Gregory S. Wallace,1 Cecilia Cheng-Mayer,2 Marco L. Schito,3,{dagger} Patricia Fletcher,1 Lisa M. Miller Jenkins,3 Ryo Hayashi,3 A. Robert Neurath,4 Ettore Appella,3* and Robin J. Shattock1*

St George's University of London, London, United Kingdom,1 Aaron Diamond AIDS Research Center, Rockefeller University, New York, New York,2 National Cancer Institute, NIH, Bethesda, Maryland,3 Virotech, 1496 Hemlock Farms, Hawley, Pennsylvania4

Received 22 April 2009/ Accepted 26 June 2009

Here, we report that the S-acyl-2-mercaptobenzamide thioester (SAMT) class of human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NCp7) inhibitors was able to prevent transmission of HIV-1 from infected cells, including primary cells. Furthermore, when SAMTs were introduced during an HIV-1 challenge of cervical explant tissue, inhibition of dissemination of infectious virus by cells emigrating from the tissue explants was observed. Preliminary studies using a rhesus macaque vaginal challenge model with mixed R5 and X4 simian-human immunodeficiency virus infection found that five of six monkeys were completely protected, with the remaining animal being partially protected, infected only by the R5 virus. These data suggest that SAMTs may be promising new drug candidates for further development in anti-HIV-1 topical microbicide applications.

* Corresponding author. Mailing address for Ettore Appella: 37 Convent Drive, Bethesda, MD 20892. Phone: (301) 402-4177. Fax: (301) 496-7220. E-mail: appellae{at}pop.nci.nih.gov. Mailing address for Robin J. Shattock: St George's University of London, Cranmer Terrace, Tooting, London SW170RE, United Kingdom. Phone: 44 181 725 5855. Fax: 44 181 725 3487. E-mail: shattock{at}sgul.ac.uk

{triangledown} Published ahead of print on 8 July 2009.

§ Supplemental material for this article may be found at http://jvi.asm.org/.

{dagger} Present address: Henry M. Jackson Foundation for the Advancement of Military Medicine, DAIDS, NIAID, NIH, Bethesda, MD.

Journal of Virology, September 2009, p. 9175-9182, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00820-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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