We recently identified a virucidal small molecule, PD 404,182 (PD) that disrupts HIV. PD possesses multiple attributes that make it an attractive candidate anti-HIV microbicide. PD 1) exhibits a unique mode of action � irreversible disruption of HIV through interaction with a yet unknown structural component; 2) exhibits antiviral activity against a broad range of primary HIV-isolates, HIV-2, and SIV at submicromolar to micromolar concentrations; 3) retains its antiviral activity for at least 8 hours in cell culture at 37�C prior to the addition of HIV to the cells; 4) is effective against both cell-free and cell-associated HIV and inhibits the transmission of dendritic cell-associated HIV to T cells; 5) is potent at neutral and low pH and fully active in seminal plasma and cervical fluids; 6) is extremely efficacious since less than 5 min of incubation with virus results in >99% loss of viral infectivity; 7) is non-toxic to human cells; 8) is non-toxic to the commensal bacteria Lactobacilli; 9) is specific � being ineffective against other enveloped viruses including Sindbis and Dengue virus, setting PD apart from non-specific surfactant/polyanion-based anti-HIV microbicides; 10) is viral-envelope-protein-independent; and 11) does not foster the emergence of resistant HIV variants at sub-neutralizing concentrations in cell culture for 60 days. Collectively, our data suggest that PD is a potent anti-HIV agent with a novel mode of action.

PD 404,182 as an HIV microbicide candidate

245th National Meeting (2013)

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