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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

DOI: 10.3390/ijms22168418 DOI Help

Authors: Emil Johansson (Umeå University) , Rémi Caraballo (Umeå University) , Daniel L. Hurdiss (Utrecht University) , Nitesh Mistry (Umeå University) , C. David Andersson (Umeå University) , Rebecca F. Thompson (University of Leeds) , Neil A. Ranson (University of Leeds) , Georg Zocher (University of Tübingen) , Thilo Stehle (University of Tübingen; Vanderbilt University School of Medicine) , Niklas Arnberg (Umeå University) , Mikael Elofsson (Umeå University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: International Journal Of Molecular Sciences , VOL 22

State: Published (Approved)
Published: August 2021
Diamond Proposal Number(s): 19691

Open Access Open Access

Abstract: 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.

Journal Keywords: sialic acid conjugates; antivirals; conjunctivitis; coxsackievirus A24v; 5-N-acetylneuraminic acid; multivalency; cryo-EM

Diamond Keywords: Viruses; Conjunctivitis

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 11/08/2021 08:43

Documents:
ijms-22-08418.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)