Inhibition of HIV-1 Entry: Multiple Keys to Close the Door

摘要

HIV-1 entry into target cells is a multistep time-ordered process that involves a series of consecutive interactions between the envelope glycoproteins of the virions and surface molecules on susceptible cells which ultimately results in membrane fusion and cellular uptake of virus particles. This initial step in the HIV-1 replication cycle represents an attractive target for therapeutic intervention, as entry inhibitors block the de novo infection of cells. Consequently, numerous efforts to develop compounds that target the various steps of HIV-1 entry, including attachment, binding to the CD4 receptor, binding to co-receptors CCR5 or CXCR4, and membrane fusion, have resulted in distinct classes of entry inhibitors, two of which have already been approved by the US Food and Drug Administration (FDA) for the treatment of HIV-positive patients. Herein we review the different compound classes under development or at various clinical trial phases that target the individual steps of HIV-1 entry; these include peptides, antibodies, natural products, and small molecules.