Taq-Man PCR analysis showed a dose-dependent inhi- bition of HCV RNA replication after treatment with 17-AAG. The 17-AAG-mediated HCV replication inhibition is due to the directly interaction of Hsp90 and NS3 by immunoprecipitation. These results have exciting implications for the HCV life cycle and novel antiviral strategies. doi:  heparin 10.1016/j.antiviral.2007.01.094 87 Development of Anti-Infective Topical Microbicides 2. Quantifying Inhibition of Virus Transmission in Microbi- cidal Setting Karen Watson ?, Lu Yang, Robert Buckheit Jr. ImQuest BioSciences, Inc., Frederick, MD, USA Over 25 million people have died since the st case of AIDS was identid in 1981, and the number of people living with HIV worldwide continues to expandrom 35 million in 2001 to an estimated 40 million in 2005. In the absence of a fully effective HIV vaccine, topical microbicides represent an impor- tant potential strategy for preventing the transmission of HIV through sexual intercourse, the predominant mode of HIV trans- mission worldwide. Although a comprehensive understanding of HIV transmission has not yet emerged, it is currently thought that virus transmission occurs rapidly and is likely the result of infection of monocyte-derived cells in the vaginal mucosa by CCR5-tropic viruses.

Transmission of virus in the microbicide setting will require agents which prevent virus entry, fusion, reverse transcription, or other pre-integrative events, or agents which directly inactivate HIV or modulate the target cells to ren- der them uninfectable. In vitro assays which are typically utilized to evaluate the ability of a microbicide to prevent virus transmis- sion utilize adherent cells (MAGI or GHOST cells) or cells more relevant to the heparin 9041-08-1 development of anti-HIV therapeutics (PBMCs) and quantify virus production following transmission at short time intervals following infection. We have modid a virus sterilization assay to evaluate virus transmission over the course of 30 days of culture in the presence and absence of microbi- cidal compounds. These assays effectively demonstrate that the transmission inhibition capacity of microbicides is dramatically over-estimated in the short-term assays. Data obtained in this microbicidal transmission assay dee the concentration of the microbicide required to completely prevent the transmission of virus to target cells and is likely the minimal concentration of the microbicide that will need to be provided in a al formu- lated product.

Further the assay can be used to dee the effects of viral multiplicity of infection and the effects of rare pop- ulations of resistant virus strains on transmission events. The results of our studies with a variety of potential microbicides being developed in our buy heparin laboratories will be presented. doi: 10.1016/j.antiviral.2007.01.095 88 Development of Anti-Infective Topical Microbicides 1. Effects of Seminal and Vaginal Fluids and Other Additives on Viral Infection and Drug Efacy Karen Watson ?, Lu Yang, Robert Buckheit Jr. ImQuest BioSciences, Inc., Frederick, MD, USA Over 25 million people have died since the st case of AIDS was identid in 1981, and the number of people living with HIV worldwide continues to expand from 35 million in 2001 to an estimated 40 million in 2005. Almost 5 million people worldwide became newly infected with HIV and an estimated 3.8 million human deaths were attributed to AIDS in 2005. In the absence of a fully effective HIV vaccine, topical microbi- cides represent an important potential strategy for preventing the transmission of HIV through sexual intercourse, the pre- dominant mode of HIV transmission worldwide.

The number of women with HIV infection and AIDS has been increasing steadily erythorbate worldwide, accounting for 46% of all adults living with HIV worldwide, and for 57% in sub-Saharan Africa. Thus the dynamics of the epidemic demand the development of safe, effective and acceptable female-controlled chemical and phys- ical barri