Respiratory syncytial virus RNA-dependent RNA polymerase L protein (RSV L protein)

The Respiratory syncytial virus (RSV) RNA-dependent RNA polymerase L protein is a large, multifunctional enzyme that serves as the catalytic core of the viral replication complex (UniProt P03422). It is responsible for the synthesis of viral messenger RNA (transcription) and the production of full-length genomic and antigenomic RNA (replication) (Gilman et al., 2019, PMID: 31160587). The L protein possesses several distinct enzymatic activities, including RNA-directed RNA polymerase activity, mRNA capping via its polyribonucleotidyltransferase domain, and cap methylation (Cao et al., 2021, PMID: 33408244). Because this enzyme is essential for viral survival and lacks a direct human homolog, it is a primary target for the development of small-molecule antivirals. Therapeutic strategies include nucleoside analogs like Lumicitabine that act as chain terminators and non-nucleoside inhibitors like PC786 that bind to allosteric sites to disrupt the enzyme's function (ClinicalTrials.gov NCT02239224). Targeting the L protein aims to reduce viral load and alleviate the clinical symptoms of RSV-associated bronchiolitis and pneumonia, particularly in high-risk populations such as infants and the elderly.

Other names

RSV LLarge proteinRNA-directed RNA polymerase LRSV RdRpL protein

Inhibition of viral RNA synthesis through nucleoside-mediated chain termination or non-nucleoside allosteric inhibition of the polymerase complex.