Pentavalent sialic acid conjugates block coxsackievirus A24 variant and human adenovirus type 37 – viruses that cause highly contagious eye infections

DOI: 10.1021/acschembio.0c00446

Authors: Emil Johansson (Umeå University) , Rémi Caraballo (Umeå University) , Nitesh Mistry (Umeå University) , Georg Zocher (University of Tübingen) , Weixing Qian (Umeå University) , C. David Andersson (Umeå University) , Daniel L. Hurdiss (Utrecht University) , Naresh Chandra (Umeå University) , Rebecca Thompson (University of Leeds) , Lars Frängsmyr (Umeå University) , 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: Acs Chemical Biology

State: Published (Approved)
Published: August 2020

Abstract: 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.

Journal Keywords: Infectious diseases; Ligands; Inhibitors; Screening assays; Conjugate acid-base pairs

Diamond Keywords: Conjunctivitis; Viruses

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 01/09/2020 09:10

Documents:
acschembio.0c00446.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)