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Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37 – Viruses That Cause Highly Contagious Eye Infections

preprint
submitted on 17.04.2020, 15:29 and posted on 20.04.2020, 11:52 by Emil Johansson, Rémi Caraballo, Nitesh Mistry, Georg Zocher, Weixing Qian, C. David Andersson, Daniel L. Hurdiss, Naresh Chandra, Rebecca Thompson, Lars Frängsmyr, thilo stehle, Niklas Arnberg, Mikael Elofsson
Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection, and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.

Funding

Knut and Alice Wallenberg Foundation, Baden-Württemberg Foundation, Glycobiology program

History

Email Address of Submitting Author

mikael.elofsson@umu.se

Institution

Umeå University

Country

Sweden

ORCID For Submitting Author

0000-0002-3219-4669

Declaration of Conflict of Interest

The authors declare no conflict of interest.

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