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The Suramin Derivative NF449 Interacts with the 5-fold Vertex of the Enterovirus A71 Capsid to Prevent Virus Attachment to PSGL-1 and Heparan Sulfate


Enterovirus A71 is epidemic in the Asia-Pacific region, and has been responsible for thousands of cases of fatal neurological disease in young children. There are no specific therapies available. We previously identified NF449 as a compound with anti-EV-A71 activity, although its mechanism of action was uncertain. In the current work we found that NF449 and related molecules prevent virus attachment both to PSGL-1, a receptor molecule important for virus interaction with white blood cells, and to heparan sulfate, a receptor that may be important for virus interaction with a variety of other cell types. In contrast, we found that NF449 had no effect on virus attachment to another proposed receptor, SCARB2. We also found that NF449 and related compounds interact with a specific site on the viral capsid, remote from the binding site for another major receptor, SCARB2. Our work provides information that may facilitate development of improved antiviral compounds that block the attachment of EV-A71 to cellular receptors.


Vyšlo v časopise: The Suramin Derivative NF449 Interacts with the 5-fold Vertex of the Enterovirus A71 Capsid to Prevent Virus Attachment to PSGL-1 and Heparan Sulfate. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005184
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005184

Souhrn

Enterovirus A71 is epidemic in the Asia-Pacific region, and has been responsible for thousands of cases of fatal neurological disease in young children. There are no specific therapies available. We previously identified NF449 as a compound with anti-EV-A71 activity, although its mechanism of action was uncertain. In the current work we found that NF449 and related molecules prevent virus attachment both to PSGL-1, a receptor molecule important for virus interaction with white blood cells, and to heparan sulfate, a receptor that may be important for virus interaction with a variety of other cell types. In contrast, we found that NF449 had no effect on virus attachment to another proposed receptor, SCARB2. We also found that NF449 and related compounds interact with a specific site on the viral capsid, remote from the binding site for another major receptor, SCARB2. Our work provides information that may facilitate development of improved antiviral compounds that block the attachment of EV-A71 to cellular receptors.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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