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Mesquita, Pedro M.*
Herold, B.**, Shattock, R.J.*
*St. Georges Hospital Medical School, London, UK. Department of Cellular and Molecular Medicine, Division of Infectious Diseases**Mount Sinai School of Medicine, New York, USA. Department of Medicine, Division of Infectious Diseases
Background
Epidemiological data show that HSV-2 infection of the genital tract is very common among HIV-1 +ve patients and enhances HIV-1 acquisition. Consequently, it is important to develop topical microbicides that block transmission of both viruses. SAMMA (mandelic acid condensation polymer) is a potentially cheap and effective microbicide against HIV-1, HSV-2 and several other STDs. Its precursor, mandelic acid, has a long history of safe usage in humans, having been utilised as a urinary antiseptic. We have investigated the activity of SAMMA against HIV-1(R5 and X4) and HSV-2 using cellular and human cervical explant models.
Methods.
Anti-HIV-1 and anti-HSV-2 activity of SAMMA was evaluated in human cervical explants, human monocyte derived macrophages and other cell lines. Blockade of DC-SIGN mediated HIV-1 infection was investigated using THP-1/DC-SIGN transfectants and biocompatibility was assessed using viability assays and cytokine profiles from mucosal tissue exposed to SAMMA and Nonoxynol-9 as a control.
Results
Our data show that SAMMA potently inhibits HIV-1 activity across a variety of strains both as cell free and cell associated virus. It inhibits trans infection via DC-SIGN in cellular models and, in addition, it shows strong inhibition of HSV-2 infection and good tissue biocompatibility.
Conclusions
SAMMA has shown strong anti-viral activity against both HIV and HSV in cellular, macrophage and cervical explant models and is biocompatible at the concentrations tested. These data along with its established safety record and low manufacture costs make it an ideal candidate for further development as a topical microbicide.
Mr. Pedro Mesquita
St. Georges Hospital Medical School, Dept. Cellular and Molecular Medicine, room 2.128, Jenner wing
(Telephone) 02087251603 (Fax) 02087253487 (E-mail) pmesquit@sghms.ac.uk
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