Through screening by NMR spectroscopy, we discovered a novel scaffold (DPQ: 6,7-dimethoxy-2-(1-piperazinyl)-4-quinazolinamine) that binds specifically to the influenza A virus promoter RNA. The solution structure of the RNA-DPQ complex reported here demonstrates that the internal loop is the binding site of DPQ. The scaffold has antiviral activity against influenza viruses.
Aminoglycosides bind to the influenza A virus promoter (vRNA) at submicromolar concentration. The complex structure between the vRNA and neomycin illustrates that binding of neomycin causes a conformational change which would affect further transcription processes. Thus, aminoglycosides represent lead compounds for the discovery of antiviral therapeutics against influenza A virus.
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