Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus
Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-03-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/11/3/242 |
| _version_ | 1811210868376993792 |
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| author | Naresh Chandra Lars Frängsmyr Niklas Arnberg |
| author_facet | Naresh Chandra Lars Frängsmyr Niklas Arnberg |
| author_sort | Naresh Chandra |
| collection | DOAJ |
| description | Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development. |
| first_indexed | 2024-04-12T05:02:55Z |
| format | Article |
| id | doaj.art-c679bf9266b64c2cada76d10a9c32649 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-12T05:02:55Z |
| publishDate | 2019-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-c679bf9266b64c2cada76d10a9c326492022-12-22T03:46:57ZengMDPI AGViruses1999-49152019-03-0111324210.3390/v11030242v11030242Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human AdenovirusNaresh Chandra0Lars Frängsmyr1Niklas Arnberg2Section of Virology, Department of Clinical Microbiology, Umeå University, SE-90185 Umeå, SwedenSection of Virology, Department of Clinical Microbiology, Umeå University, SE-90185 Umeå, SwedenSection of Virology, Department of Clinical Microbiology, Umeå University, SE-90185 Umeå, SwedenEpidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development.http://www.mdpi.com/1999-4915/11/3/242glycosaminoglycansadenoviruscellular receptordecoy receptorepidemic keratoconjunctivitisGAG-mimetic |
| spellingShingle | Naresh Chandra Lars Frängsmyr Niklas Arnberg Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus Viruses glycosaminoglycans adenovirus cellular receptor decoy receptor epidemic keratoconjunctivitis GAG-mimetic |
| title | Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus |
| title_full | Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus |
| title_fullStr | Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus |
| title_full_unstemmed | Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus |
| title_short | Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus |
| title_sort | decoy receptor interactions as novel drug targets against ekc causing human adenovirus |
| topic | glycosaminoglycans adenovirus cellular receptor decoy receptor epidemic keratoconjunctivitis GAG-mimetic |
| url | http://www.mdpi.com/1999-4915/11/3/242 |
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