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Exploring the effect of structure-based scaffold hopping on the inhibition of coxsackievirus a24v transduction by pentavalent n-acetylneuraminic acid conjugates
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Virology Section, Infectious Diseases and Immunology Division, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Section of Virology.
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2021 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 16, article id 8418Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2021. Vol. 22, no 16, article id 8418
Keywords [en]
5-N-acetylneuraminic acid, Antivirals, Conjunctivitis, Coxsackievirus A24v, Cryo-EM, Multivalency, Sialic acid conjugates
National Category
Microbiology in the medical area Immunology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-186555DOI: 10.3390/ijms22168418ISI: 000689130700001Scopus ID: 2-s2.0-85111762142OAI: oai:DiVA.org:umu-186555DiVA, id: diva2:1584374
Available from: 2021-08-11 Created: 2021-08-11 Last updated: 2023-09-05Bibliographically approved

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Johansson, EmilCaraballo, RemiMistry, NiteshAndersson, C. DavidArnberg, NiklasElofsson, Mikael

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International Journal of Molecular Sciences
Microbiology in the medical areaImmunology in the medical area

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