A new approach to protecting human cells from viral infection (after infection) is described for the virus VSV, closely related to RSV and parainfluenzavirus. The active compound stabilizes the complex between viral RNA and its protein coat, preventing viral replication. An X-ray crystal structure shows a unique position for the compound that locks the viral RNA and protein together.
New and improved drugs are needed to fight respiratory infections caused by negative-strand RNA viruses. This work may provide a starting point for optimizing drug candidates that will transfer from VSV to RSV and other clinically-important respiratory viruses.
It is important to find a new compound class active against negative-strand RNA viruses, especially one not expected to bind tightly to RNA. Here, we see a polyamide binding simultaneously to RNA and protein and doing so strongly enough to break open the traditional "hairpin" structure so that there is, uniquely, no pi-stacking among polyamide heterocycles. Much work needs to be done to develop this initial discovery.Dr. James Bashkin, D. Phil.
J Virol 2018 04 28;92(8). Epub 2018 Mar 28.
Department of Chemistry, Georgia State University, Atlanta, Georgia, USA
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