Inhibitors for de novo-RNA polymerases and methods of identifying targets for same

A polymerase inhibitor has first moiety coupled to a second moiety via an optional linker in which the first moiety binds to an initiation nucleotide binding site of a polymerase and forms at least two hydrogen bonds with an RNA template strand that is associated with the polymerase, and in which the second moiety comprised a compound that binds to a site proximal to the nucleotide binding site of the polymerase and thereby increases the affinity of the polymerase inhibitor to the polymerase.