What is it about?

A small molecule, known a pyrrole-imidazole-based polyamide, was found to inhibit Vesicular Stomatitis Virus (VSV) infections in cells. The crystal structure of the small molecule inhibitor was determined bound to RNA and a nucleocapsid-like particle. The structure shows that the active compound is bound to both RNA and protein. Biophysical measurements indicated that the melting temperature (stability) of the nucleocapsid-like particle (NLP) was affected by the presence of the active compound. Interestingly, polyamides were previously reported to bind poorly to RNA by two groups.

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Why is it important?

This is the first example of a polyamide acting against the RNA of an RNA virus rather than a subsequent DNA form. VSV is a model for other viruses that are clinically important.

Perspectives

Negative strand RNA viruses include many respiratory viruses, such as RSV and parainfluenza virus. RSV is responsible for vast numbers of infant hospitalizations and can be fatal to the very young and the elderly. We hope to develop our initial results into a general approach that is entirely novel against these dangerous diseases.

Professor James Keane Bashkin
University of Missouri-St. Louis

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This page is a summary of: A Polyamide Inhibits Replication of Vesicular Stomatitis Virus by Targeting RNA in the Nucleocapsid, Journal of Virology, February 2018, ASM Journals,
DOI: 10.1128/jvi.00146-18.
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