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Updated: Jun 25, 2026

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
Bacterial RNA polymerase inhibitors: an organized overview of their structure, derivatives, biological activity and
1Gentium Spa, Piazza XX Settembre 2, 22079 Villa Guardia (CO), Italy. marianiriccardo@gmail.com
Abstract:
RNA polymerase (RNAP) currently represents an important target for the development of new antibacterial agents. RNAP is a nucleotidyl transferase enzyme able to generate an RNA copy of a DNA or RNA template chain, controlling initiation and termination of transcription. RNAP is found in nature in all eukaryotes, prokaryotes and archaea, as well as in many viruses. Bacterial RNAP is a large molecule (about 400 kDa) and its core structure is composed of four polypeptide subunits: alpha (alpha) required for assembly of the enzyme, beta (beta) involved in chain initiation and elongation, beta' (beta') which binds to the DNA template, and omega (omega) which constrains the beta' subunit and aids its assembly into RNAP, in the stoichiometry alpha2betabeta'omega. The bacterial enzyme differs both from eukaryotic RNAP, which is composed of different subunits and is present in several variants, and from archaeal or viral RNAP. These differences allow to selectively target the bacterial enzyme with appropriately designed inhibitors, excluding interactions with eukaryotic RNAP, accounting for the deep interest developed around these compounds as selective antibacterial agents. In this review the known natural and synthetic inhibitors of RNAP will be described considering their mechanism of action, biological activity, availability of analogues, Structure Activity Relationship (SAR) information and clinical use when already approved or recently entered into clinical trials.
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