A multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus

Varga, Norbert; Sutkevičiūtė, Ieva; Ribeiro-Viana, Renato; Berzi, Angela; Ramdasi, Rasika; Daghetti, A.; Vettoretti, Gerolamo; Amara, Ali; Clerici, Mario; Rojo, Javier; Fieschi, Franck; Bernardi, Anna

doi:10.1016/j.biomaterials.2014.01.014

Cited by 111 publications

(123 citation statements)

References 40 publications

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“…While IC 50 in the low micromolar range are achieved already for hexavalent constructs using the most powerful ligand 33, the other mannosylated and pseudomannosylated dendrimers are significanty less effective, even at higher valency. The hexavalent presentation of 33 in dendrimer 36 provided 100% inhibition of trans HIV infection at 10 µM concentration in a cellular model [73] and stimulated early immune response from DCs [74].…”

Section: Figurementioning

confidence: 99%

“…Compound 33 ( Figure 5) was selected among them for the synthesis of dendrimers based on an erythritol core, that were tested for DC-SIGN binding (SPR inhibition assay) and compared to the corresponding versions bearing mannose or 30 [73]. Dendrimers up to the valency of 18 were synthesized; representative structures are shown in Figure 5 (34-36).…”

Section: Figurementioning

confidence: 99%

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Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives

Sattin

Bernardi

2016

Trends in Biotechnology

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Microbial adhesion is an essential step of infections and is mediated primarily by proteincarbohydrate interactions. Antagonists of such interactions have become a promising target for antiadhesive therapy in a number of infective diseases. Monovalent protein-sugar interactions are often weak, and most successful antiadhesive materials consist of multivalent glycoconjugates.Although often very effective in hampering microbial adhesion, natural epitopes often show limited resistance to enzymatic degradation. The use of carbohydrate mimics (glycomimetics) as a replacement for natural sugars potentially allows to achieve higher metabolic stability and also higher selectivity towards the desired protein target. In this review we will describe the state of the art on the design and synthesis of glycoconjugates and glycomimetics employed for the construction of antiadhesive biomaterials.

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confidence: 99%

Section: Figurementioning

confidence: 99%

Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives

Sattin

Bernardi

2016

Trends in Biotechnology

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“…12 Inhibitors of HIV infection and transinfection via the DC-SIGN lectin receptor have been tested only in preclinical studies. [13][14][15] Development or application of known drugs for the inhibition of HIV/DC-SIGN interaction may help in decreasing transinfection of T cells and in preventing the infection of DCs that serve as a long-term reservoir of HIV.…”

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confidence: 99%

“…DC-SIGN inhibitors are of special interest as a means of preventing DC infection and CD4 + T cell transinfection by HIV. Many potential DC-SIGN inhibitors are in various stages of research, [13][14][15] and approaches for the high-throughput screening of potential inhibitors are being developed. 37 Our earlier studies on human macrophages 38 demonstrate that dextrans are also inhibitors of the interaction of HIV with another C-type lectin MR (CD206).…”

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confidence: 99%

Short Communication: Inhibition of DC-SIGN-Mediated HIV-1 Infection by Complementary Actions of Dendritic Cell Receptor Antagonists and Env-Targeting Virus Inactivators

Pustylnikov

Dave

Khan

et al. 2016

AIDS Research and Human Retroviruses

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The DC-SIGN receptor on human dendritic cells interacts with HIV gp120 to promote both infection of antigenpresenting cells and transinfection of T cells. We hypothesized that in DC-SIGN-expressing cells, both DC-SIGN ligands such as dextrans and gp120 antagonists such as peptide triazoles would inhibit HIV infection with potential complementary antagonist effects. To test this hypothesis, we evaluated the effects of dextran (D66), isomaltooligosaccharides (D06), and several peptide triazoles (HNG156, K13, and UM15) on HIV infection of B-THP-1/DC-SIGN cells. In surface plasmon resonance competition assays, D66 (IC 50 = 35.4 lM) and D06 (IC 50 = 3.4 mM) prevented binding of soluble DC-SIGN to immobilized mannosylated bovine serum albumin (BSA). An efficacious dose-dependent inhibition of DC-SIGN-mediated HIV infection in both pretreatment and posttreatment settings was observed, as indicated by inhibitory potentials (EC 50 ) [D66 (8 lM), D06 (48 mM), HNG156 (40 lM), UM15 (100 nM), and K13 (25 nM)]. Importantly, both dextrans and peptide triazoles significantly decreased HIV gag RNA levels [D66 (7-fold), D06 (13-fold), HNG156 (7-fold), K-13 (3-fold), and UM15 (6-fold)]. Interestingly, D06 at the highest effective concentration showed a 14-fold decrease of infection, while its combination with 50 lM HNG156 showed a 26-fold decrease. Hence, these compounds can combine to inactivate the viruses and suppress DC-SIGN-mediated virus-cell interaction that as shown earlier leads to dendritic cell HIV infection and transinfection dependent on the DC-SIGN receptor.

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“…Engagement of DC-SIGN results in activation of Raf-1 and phosphorylation of p65, leading to the recruitment of the transcription elongation factor pTEF-b to the HIV-1 transcription complex and subsequent generation of full-length HIV-1 transcripts (Gringhuis et al, 2010). Interestingly, DC-SIGN targeting by glycodendrimers bearing carbohydrates or glycomimetic DC-SIGN ligands led to the identification of a product that inhibits DC-SIGN-mediated infection of T cells by HIV-1 and uptake of Dengue virus by Raji cells (Varga et al, 2014).…”

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confidence: 99%