Lassa virus RNA-directed RNA polymerase L (LASV L)

The Lassa virus RNA-directed RNA polymerase L, commonly referred to as the L protein, is a massive, multi-domain enzyme that is essential for the replication and transcription of the Lassa virus (LASV) genome. As a member of the Arenaviridae family, the L protein performs several critical enzymatic activities, including RNA-dependent RNA polymerase activity for genome duplication and an N-terminal endonuclease activity used for 'cap-snatching'—a process where the virus steals 5' caps from host cellular mRNAs to prime its own transcription (UniProt: P13697). Because the L protein is the central engine of viral production and lacks a direct human counterpart, it serves as a high-priority target for antiviral therapeutics (PubMed: 32572031). In the context of Lassa fever, which can cause severe hemorrhagic symptoms and high mortality, targeting the L protein is one of the few viable clinical strategies. Current treatments like Ribavirin and investigational drugs like Favipiravir act as nucleoside analogs that are incorporated by the L protein into nascent RNA strands, eventually stalling replication or inducing a catastrophic error rate in the viral population (PubMed: 25413340). Despite its importance, the high mutation rate of the virus poses a significant challenge to long-term drug efficacy and the development of resistant strains.

Other names

Lassa virus RNA-dependent RNA polymeraseL proteinRNA-directed RNA polymerase LLASV RdRpLassa virus L polymerase

Inhibition of viral RNA synthesis through nucleoside or nucleotide analog competition with natural substrates, leading to premature chain termination or lethal mutagenesis of the viral genome.