A glycomimetic compound inhibits DC-SIGN-mediated HIV infection in cellular and cervical explant models

Abstract

Dendron 12 thus inhibits HIV-1 infection by competition with binding of HIV to DC-SIGN and stimulation of β-chemokine production. Dendron 12 represents a promising lead compound for the development of anti-HIV topical microbicides.

Bifunctional CD4–DC-SIGN Fusion Proteins Demonstrate Enhanced Avidity to gp120 and Inhibit HIV-1 Infection and Dissemination

“…The interaction of HIV-1 with DC-SIGN does not result in direct infection of DCs but instead enhances cis and/or trans infection. Several studies have shown that antagonists against DC-SIGN inhibit DC-SIGN-mediated HIV-1 transmission (7,42,46), whereas the antiviral activity of sDC-SIGN seems more complex (25,40). Although sDC-SIGN decreases the capture of HIV-1 by DC-SIGN (39), sDC-SIGN binding to HIV-1 Env can also increase the exposure of the CD4 binding site on gp120, which in turn contributes to enhancement of infection (25), compromising the development of DC-SIGN as a single agent.…”

Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives

“…They both contain a terminal mannose residue connected to a conformationally locked cyclohexanediol [67] that mimics a mannose unit -α-1,2-substituted. Both 30 and 31 bind to the Ca ++ ion in DC-SIGN binding site using the non-reducing end residue (X-ray: [68,69]), inhibit DC-SIGN binding to mannosylated BSA [70], display a measurable selectivity [68,71] against Langerin, are not cyototoxic and are active in the Ebola infection model. The pseudo-trisaccharide 31 was the first of these antagonists to be formulated in polyvalent presentations: the tetravalent-Boltorn-type dendron 32 in low micromolar concentrations was shown to block DC-SIGN mediated HIV infection both in cellular and cervical explant models [70,71].…”

Exploitation of Glycobiology in Anti-Adhesion Approaches against Biothreat Agents

“…However, mortality rate is extremely high, ranging from 30% to 90%, depending on the virus type and estimation methodologies. The WHO reported cases in the West African countries during the recent 2013-2016 outbreak were in a total of 28,657 suspected cases and 11,325 deaths, yielding 40% mortality rate [55,56]. Ebola virus entry into target cells is mediated by a single viral surface glycoprotein GP [57].…”

“…A recombinant dimeric DC-SIGN was blocked by oligomannose dendron with IC 50 values in the nanomolar range [53]. Moreover, nanoparticles bearing mannose dendrimer mimics and a high mannose dendrimer were used for blocking DC-SIGN mediated HIV infection in cellular and human uterine cervix explant models [54,55]. The incorporation of 1,2-mannobioside epitopes into gold glyconanoparticles (Au-GNPs) with valencies up to 50 or 60 copies completely inhibited the interaction of DC-SIGN with gp120 [54].…”