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- W2043559051 abstract "The interaction between HIV gp120 and galactose-containing cell surface glycolipids such as GalCer or Gb3 is known to facilitate HIV binding to both CD4+ as well as CD4− cells. In an effort to develop small molecule HIV-1 entry inhibitors with improved solubility and efficacy, we have synthesized a series of C-glycoside analogs of GalCer and tested their anti HIV-1 activity. The analogs were tested for gp120 binding using a HIV-1 (IIIB) V3-loop specific peptide. Two of the six analogs that interfered with gp120 binding also inhibited HIV Env-mediated cell-to-cell fusion and viral entry in the absence of any significant cytotoxicity. Analogs with two side chains did not show inhibition of fusion and/or infection under identical conditions. The inhibition of virus infection seen by these compounds was not coreceptor dependent, as they inhibited CXCR4, CCR5 as well as dual tropic viruses. These compounds showed inhibition of HIV entry at early steps in viral infection since the compounds were inactive if added post viral entry. Temperature-arrested state experiments showed that the compounds act at the level of virus attachment to the cells likely at a pre-CD4 engagement step. These compounds also showed inhibition of VSV glycoprotein-pseudotyped virus. The results presented here show that the glycoside derivatives of GalCer with simple side chains may serve as a novel class of small molecule HIV-1 entry inhibitors that would be active against a number of HIV isolates as well as other enveloped viruses." @default.
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- W2043559051 date "2008-10-01" @default.
- W2043559051 modified "2023-10-14" @default.
- W2043559051 title "Glycoside analogs of β-galactosylceramide, a novel class of small molecule antiviral agents that inhibit HIV-1 entry" @default.
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- W2043559051 doi "https://doi.org/10.1016/j.antiviral.2008.04.004" @default.
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