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TitleExploring the Effect of Structure-Based Scaffold Hopping on the Inhibition of Coxsackievirus A24v Transduction by Pentavalent N-Acetylneuraminic Acid Conjugates.
Journal, issue, pagesInt J Mol Sci, Vol. 22, Issue 16, Year 2021
Publish dateAug 5, 2021
AuthorsEmil Johansson / Rémi Caraballo / Daniel L Hurdiss / Nitesh Mistry / C David Andersson / Rebecca F Thompson / Neil A Ranson / Georg Zocher / Thilo Stehle / Niklas Arnberg / Mikael Elofsson /
PubMed AbstractCoxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics ...Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin.
External linksInt J Mol Sci / PubMed:34445134 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.78 - 2.3 Å
Structure data

EMDB-13025:
Coxsackievirus A24v in complex with a pentavalent N-acetylneuraminic acid conjugate
Method: EM (single particle) / Resolution: 2.3 Å

PDB-7oj7:
Crystal structure of human coxsackievirus A24v in complex with a pentavalent N-acetylneuraminic acid conjugate
Method: X-RAY DIFFRACTION / Resolution: 1.78 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-CL:
Unknown entry

ChemComp-0H0:
Carbohydrate component from a pentavalent N-acetylneuraminic acid conjugate

ChemComp-HOH:
WATER

Source
  • coxsackievirus a24
KeywordsVIRUS / human Coxsackievirus A24v / starfish-like inhibitor / corannulene

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