Tagonist `Compound A' [4-nitrobenzyl 1-(3(N-methylphenylsulfonamido)-3-phenylbutyl)piperidin-4-yl(vinyl)carbamate] [41,42] was kindly provided by Dr. Martin Springer at Merck Research Laboratories, Rahway, NJ. The anti-gp120 monoclonal antibody 48d, which recognizes an epitope that overlaps the coreceptor-binding site, was kindly provided by Dr. James Robinson (Tulane University Medical Center) [4
L limited by the lack of tools that enable monitoring of this dynamic multi-step process. Detection of conformational intermediates is largely based on the use of conformation-specific fusion/entry inhibitors, which are added at different times after initiation of the fusion process [34?38]. Although such assays have provided insights into the mechanisms of gp41-directed inhibitors, they fail to d
Ied [31,32]. These compounds, which include the prototypic compound NBD556 and its derivatives, mimic the effects of CD4 by inducing the exposure of the coreceptor-binding site on gp120 [31,33]. Although NBD-556 inhibits HIV-1 infection of CD4+CCR5+ cells, it can replace CD4 and thus enhance HIV-1 infection of CD42CCR5+ cells [31]. In view of their capacity to enhance infectivity, any potential ap
Port, we show that soluble mimics of CD4 inhibit HIV-1 infection by prematurely triggering the viral envelope glycoproteins. The unstable activated state of the virus lasts only a few minutes, after which the virus loses the ability to infect cells. This novel strategy for inhibition may be generally applicable to other viruses besides HIV-1, some of which are also activated by binding to their re
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