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Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Sialic acid is a cellular receptor for coxsackievirus A24 variant, an emerging virus with pandemic potential
Emma C Nilsson1, Fariba Jamshidi, Susanne M C Johansson
1Department of Clinical Microbiology, Division of Virology, Umeå University, Umeå SE-901 85, Sweden.
Abstract:
Binding to target cell receptors is a critical step in the virus life cycle. Coxsackievirus A24 variant (CVA24v) has pandemic potential and is a major cause of acute hemorrhagic conjunctivitis, but its cellular receptor has hitherto been unknown. Here we show that CVA24v fails to bind to and infect CHO cells defective in sialic acid expression. Binding of CVA24v to and infection of corneal epithelial cells are efficiently inhibited by treating cells with a sialic acid-cleaving enzyme or sialic acid-binding lectins and by treatment of the virus with soluble, multivalent sialic acid. Protease treatment of cells efficiently inhibited virus binding, suggesting that the receptor is a sialylated glycoprotein. Like enterovirus type 70 and influenza A virus, CVA24v can cause pandemics. Remarkably, all three viruses use the same receptor. Since several unrelated viruses with tropism for the eye use this receptor, sialic acid-based antiviral drugs that prevent virus entry may be useful for topical treatment of such infections.
Insights
Coxsackievirus A24 variant uses sialic acid as its cellular receptor, a critical step for infection. This finding identifies a potential target for developing new antiviral drugs against this pandemic-potential virus.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Coxsackievirus A24 variant (CVA24v) is a significant cause of acute hemorrhagic conjunctivitis with pandemic potential.
- The cellular receptor for CVA24v has not been previously identified, hindering the development of targeted antiviral therapies.
Purpose of the Study:
- To identify the cellular receptor for Coxsackievirus A24 variant (CVA24v).
- To investigate the role of sialic acid in CVA24v binding and infection.
- To explore potential therapeutic strategies targeting the identified receptor.
Main Methods:
- Utilized Chinese Hamster Ovary (CHO) cells deficient in sialic acid expression to assess CVA24v binding and infection.
- Employed sialic acid-cleaving enzymes and sialic acid-binding lectins to inhibit CVA24v interaction with corneal epithelial cells.
- Tested the efficacy of soluble, multivalent sialic acid in blocking CVA24v infection.
- Investigated the role of proteases in CVA24v cell binding to determine receptor characteristics.
Main Results:
- CVA24v failed to bind and infect CHO cells lacking sialic acid.
- Sialic acid-cleaving enzymes, sialic acid-binding lectins, and soluble sialic acid significantly inhibited CVA24v binding and infection of corneal epithelial cells.
- Protease treatment of cells abolished CVA24v binding, indicating the receptor is a sialylated glycoprotein.
- CVA24v shares the same sialic acid receptor with Enterovirus 70 and Influenza A virus.
Conclusions:
- Sialic acid is the cellular receptor for Coxsackievirus A24 variant (CVA24v).
- CVA24v utilizes a sialylated glycoprotein as its receptor, similar to other pathogenic viruses.
- Sialic acid-based antiviral drugs hold promise for topical treatment of eye infections caused by CVA24v and other viruses using this receptor.
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