HIV-2 Susceptibility to Entry Inhibitors.
ABSTRACT Currently, there is a growing interest in using entry inhibitors to treat HIV-2-infected patients because, among the available drugs, few are fully active against HIV-2. Recent studies indicate that maraviroc and other experimental entry inhibitors, including new CCR5 and CXCR4 antagonists, inhibit primary isolates of HIV-2 as well as HIV-1 and may, therefore, expand the existing therapeutic armamentarium against HIV-2. There are, however, significant differences between the evolution of HIV-1 and HIV-2 envelope glycoproteins during infection that can lead to differences in the response to therapy with entry inhibitors over the course of the infection. Here, we review the available data on the susceptibility of HIV-2 to entry inhibitors in the context of the evolution of the sequence, structure, and function of envelope glycoproteins during infection.
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ABSTRACT: Due to resistance to all classes of anti-HIV drugs and drug toxicity, there is a need for the discovery and development of new anti-HIV drugs. HIV-1 inhibitors were identified and biologically characterized for mechanism of action. We identified a dibenzocyclooctadiene lignan, termed HDS2 that possessed anti-HIV activity against a wide variety of viral strains with EC50 values in the 1-3 µM range. HDS2 was shown to act as an NNRTI by qPCR and in vitro enzyme assays. This compound provides a new scaffold for further optimization of activity through structure-guided design. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.Antiviral chemistry & chemotherapy 02/2015; 24(1):28-38. DOI:10.1177/2040206614566580