RNA polymerase (RNAP) (RNAP)

RNA polymerase (RNAP) is the central enzyme complex responsible for the synthesis of RNA from a DNA or RNA template, a process essential for gene expression and viral replication. In bacteria, the DNA-directed RNA polymerase is a multi-subunit complex that serves as the primary target for the rifamycin class of antibiotics, which bind to the beta subunit to sterically hinder the elongation of the nascent RNA chain [1]. In the context of RNA viruses, the RNA-dependent RNA polymerase (RdRp) is the core component of the viral replication-transcription machinery, making it a high-priority target for antiviral therapy [2]. Drugs such as remdesivir and sofosbuvir are nucleoside analogs that target the RdRp, acting as chain terminators that halt viral genome synthesis [3]. While eukaryotic RNA polymerases (Pol I, II, and III) are generally avoided as targets due to potential systemic toxicity, they are increasingly scrutinized in oncology for their role in driving the rapid growth of cancer cells [5]. The structural and functional diversity between prokaryotic, viral, and eukaryotic polymerases provides the basis for the selective toxicity required for effective antimicrobial and antiviral drug development.

Other names

RNA polymerase complexRNA synthesis machineryTranscriptaseDNA-directed RNA polymeraseRNA-dependent RNA polymerase (RdRp)Replication-transcription complex (RTC)

Inhibition of RNA synthesis through various mechanisms including steric blocking of the RNA exit channel (e.g., rifamycins), competitive inhibition of nucleotide binding, or acting as a nucleoside analog to cause premature chain termination (e.g., remdesivir, sofosbuvir) [1, 2, 3].