Respiratory syncytial virus RNA-directed RNA polymerase L protein (L protein)

The **Respiratory syncytial virus RNA-directed RNA polymerase L protein** (L protein) is a large (~250 kDa) multifunctional enzyme that is a critical component of the RSV polymerase complex. It possesses three major domains with distinct functions: the **RNA-dependent RNA polymerase (RdRp)** domain for viral genome and antigenome replication and transcription, a **capping (Polyribonucleotidyl transferase; PRNTase)** domain for mRNA cap addition, and a **methyltransferase (MTase)** domain for cap methylation[1][3][8]. The L protein also carries out the polyadenylation of subgenomic viral mRNAs[2]. To function, L forms a complex with a tetrameric phosphoprotein (P), which stabilizes the enzyme and interacts with the encapsidated viral RNA. This complex catalyzes all steps required for RSV RNA synthesis and mRNA processing, making it essential for viral replication and an attractive **antiviral drug target**[1][3][4][7]. Small molecule inhibitors, such as **ALS-8176 (lumicitabine)** and other RSV polymerase inhibitors, are being developed against L protein, targeting either polymerase or capping activities[4]. Resistance can arise through mutations in L, underscoring the need for structure-guided inhibitor development[4].

Other names

RSV L proteinLarge polymerase subunitRNA-dependent RNA polymerase L proteinRSV L

Inhibition of RNA synthesis (via targeting RNA polymerase active site or interfering with capping/methylation domains)[4][1] Chain termination by nucleoside analogs[4]