RNA-directed RNA polymerase L (RdRp L)

The RNA-directed RNA polymerase L, commonly referred to as the L protein, is a large, multifunctional enzyme that serves as the primary replicative machinery for non-segmented negative-strand RNA viruses (Mononegavirales) and several families of segmented RNA viruses, such as Bunyavirales and Arenavirales [4, 15]. It is responsible for both the replication of the viral RNA genome and the transcription of viral messenger RNAs (mRNAs) [1, 12]. The L protein is highly complex, often containing multiple domains that execute diverse enzymatic functions, including RNA-dependent RNA polymerase (RdRp) activity, mRNA capping (via guanylyltransferase and methyltransferase domains), and polyadenylation [5, 15]. In certain viruses like Hantaviruses, it also possesses an endonuclease domain used for "cap-snatching," a process where the virus steals the 5' cap from host mRNAs to initiate its own transcription [3, 4]. Because the L protein is essential for viral survival and lacks a direct functional counterpart in human cells, it is a premier target for antiviral therapy [13, 16]. Current drug candidates include nucleoside analogs that act as chain terminators and non-nucleoside inhibitors that target allosteric sites to block enzyme activity [1, 16].

Other names

Large structural proteinReplicaseTranscriptaseL proteinRNA-dependent RNA polymerase L

Nucleoside analog-mediated chain termination, allosteric inhibition of polymerase activity, endonuclease inhibition, and methyltransferase inhibition.