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Wallace, Greg*
Jiang, S**, Watts, P*, Strick, N*, Griffin, G*, Neurath, A R** and Shattock R J*
*St Georges Hospital Medical School, London UK and **The Lindsay F Kimball Research Institute of the New York Blood Center, New York, NY, USA
HIV-1 and a number of other STDs with a long history of safe usage in humans. We have investigated CAP as a potential microbicide both as a base compound and a formulated gel against a range of HIV-1 strains and clades using cellular and human cervical explant models and in combination with zinc finger inhibitors.
Methods
Anti-HIV-1 activity of CAP and nucleocapsid p7 zinc finger inhibitors (zfi) alone and in combination was determined by in vitro assays and in ex vivo human cervical explant models. THP-1/DC-SIGN transfectants and monocyte derived dendritic cells were used to investigate the action of CAP against dendritic cell medicated infection. Biocompatibility was assessed by viability assays and cytokine profiles from mucosal tissue exposed to both compounds and N-9 as a control.
Results
Our results show that CAP strongly inhibits the activity of a number of different cell free and cell associated strains and clades of HIV-1. It inhibits viral transfer via DC-SIGN and by migratory cells emigrating from cervical explants. Furthermore, it is biocompatible and is effective in the presence of seminal plasma and across a wide pH range. Preliminary studies with zfi showed some promise for development of a combination microbicide.
Conclusions
CAP has shown strong anti-viral activity across a spectrum of HIV strains and clades in cellular, dendritic cell and cervical explant models and is biocompatible at all concentrations tested. Therefore, it shows good potential for development as a topical microbicide.
Mr Gregory Wallace
St Georges Hospital Medical School, Dept of Infectious Diseases, Cranmer Terrace, London SW17 0RE
(Tel) 020 8725 1603 (Fax) 020 8725 3487 (E-mail) gwallace@sghms.ac.uk
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