Inhibition of siRNA Binding to a p19 Viral Suppressor of RNA Silencing by Cysteine Alkylation

Eukaryotes have evolved complex cellular responses to double-stranded RNA. The quantities of short interfering RNA (siRNA) can be determined rapidly by using 96-well arrays of the carnation Italian ringspot virus (CIRV) p19 protein, which binds double-stranded siRNAs with nanomolar affinity and discriminates siRNA according to length. Two compounds were found to inhibit siRNA binding to CIRV p19 by alkylating active-site cysteine residues (see diagram).