A Potent Trivalent Sialic Acid Inhibitor of Adenovirus Type 37 Infection of Human Corneal Cells

Spjut, Sara; Qian, Weixing; Bauer, Johannes H.; Storm, Rickard; Frängsmyr, Lars; Stehle, Thilo; Arnberg, Niklas; Elofsson, Mikael

doi:10.1002/anie.201101559

Cited by 38 publications

(44 citation statements)

References 8 publications

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“…21 This clearly underlines the need of an internal reference during the SPR experiments. Due to the fast on and off rates, the association and dissociation constants could not be determined.…”

Section: Surface Plasmon Resonance (Spr) Experiments Of Selected Trivmentioning

confidence: 95%

“…21 All target compounds were ≥95% pure according to HPLC UV-traces. NMR experiments were conducted at 298 K in CDCl 3 (residual solvent peak = 7.26 ppm (δ H )), CD 3 OD (residual solvent peak = 3.31 ppm (δ H ) and 49.00 ppm (δ C )) and D 2 O (residual solvent peak = 4.79 ppm (δ H )).…”

Section: Methodsmentioning

confidence: 99%

“…§ 17,21 In all complex structures (Fig. A simultaneous binding of the three sialic acid residues from a single ligand to the same fiber knob was evidenced, and most sialic acid/Ad37 contacts observed in previous complexes 17,21,35 were retained within the different complex structures ( Fig. A simultaneous binding of the three sialic acid residues from a single ligand to the same fiber knob was evidenced, and most sialic acid/Ad37 contacts observed in previous complexes 17,21,35 were retained within the different complex structures ( Fig.…”

Section: Crystallographymentioning

confidence: 99%

“…[18][19][20][21] In order to circumvent the relatively low efficacy of monovalent sialic acid derivatives, the authors took advantage of the trimeric binding site at the Ad37 fiber knob. [18][19][20][21] In order to circumvent the relatively low efficacy of monovalent sialic acid derivatives, the authors took advantage of the trimeric binding site at the Ad37 fiber knob.…”

Section: Introductionmentioning

confidence: 99%

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Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells

et al. 2015

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Adenovirus type 37 (Ad37) is one of the principal agents responsible for epidemic keratoconjunctivitis (EKC), a severe ocular infection that remains without any available treatment. Recently, a trivalent sialic acid derivative (ME0322, Angew. Chem. Int. Ed., 2011, 50, 6519) was shown to function as a highly potent inhibitor of Ad37, efficiently preventing the attachment of the virion to the host cells and subsequent infection. Here, new trivalent sialic acid derivatives were designed, synthesized and their inhibitory properties against Ad37 infection of the human corneal epithelial cells were investigated. In comparison to ME0322, the best compound (17a) was found to be over three orders of magnitude more potent in a cell-attachment assay (IC50 = 1.4 nM) and about 140 times more potent in a cell-infection assay (IC50 = 2.9 nM). X-ray crystallographic analysis demonstrated a trivalent binding mode of all compounds to the Ad37 fiber knob. For the most potent compound ophthalmic toxicity in rabbits was investigated and it was concluded that repeated eye administration did not cause any adverse effects.

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Section: Surface Plasmon Resonance (Spr) Experiments Of Selected Trivmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Section: Crystallographymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells

et al. 2015

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“…Indeed, two types of compounds have been developed and evaluated in vitro. The first type comprises larger, protein-or lipid-based compounds with the capacity to aggregate HAdV-37 progeny and thereby limit the number of infectious units in the eye [31,32], and the other type is a smaller, trivalent compound where each SA is designed to fit into the three SA-binding sites of the knob [33,34]. The latter molecules cannot aggregate virions, but can bind virions with high-affinity, block virus attachment and thereby prevent infection at low concentrations (IC50, i.e., the concentration that reduces infection rates to 50% of controls, in low nM range).…”

Section: Sa-containing Glycansmentioning

confidence: 99%

Glycomics and Proteomics Approaches to Investigate Early Adenovirus–Host Cell Interactions

Laßwitz

Chandra

Arnberg

2018

Journal of Molecular Biology

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Adenoviruses as most viruses rely on glycan and protein interactions to attach to and enter susceptible host cells. The Adenoviridae family comprises more than 80 human types and they differ in their attachment factor and receptor usage, which likely contributes to the diverse tropism of the different types. In the past years, methods to systematically identify glycan and protein interactions have advanced. In particular sensitivity, speed and coverage of mass spectrometric analyses allow for high-throughput identification of glycans and peptides separated by liquid chromatography. Also, developments in glycan microarray technologies have led to targeted, high-throughput screening and identification of glycan-based receptors. The mapping of cell surface interactions of the diverse adenovirus types has implications for cell, tissue, and species tropism as well as drug development. Here we review known adenovirus interactions with glycan- and protein-based receptors, as well as glycomics and proteomics strategies to identify yet elusive virus receptors and attachment factors. We finally discuss challenges, bottlenecks, and future research directions in the field of non-enveloped virus entry into host cells.

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Polyvalent Transition‐State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases**

assailly

Bridot

Saumonneau

et al. 2021

Chemistry A European J

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A Potent Trivalent Sialic Acid Inhibitor of Adenovirus Type 37 Infection of Human Corneal Cells

Cited by 38 publications

References 8 publications

Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells

Triazole linker-based trivalent sialic acid inhibitors of adenovirus type 37 infection of human corneal epithelial cells

Glycomics and Proteomics Approaches to Investigate Early Adenovirus–Host Cell Interactions

Polyvalent Transition‐State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases**

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