Target intelligence / Profile preview

RNA-directed RNA polymerase L (Zaire ebolavirus) (L protein)

Target
L protein
Molecular classification
Enzyme, RNA-directed RNA polymerase
01

Overview

The RNA-directed RNA polymerase L (L protein) of the Zaire ebolavirus is a massive, multifunctional enzyme that serves as the catalytic core of the viral replication complex (UniProt P35251). It is responsible for the transcription of viral genes into messenger RNAs (mRNAs) and the replication of the negative-sense genomic RNA (Wikipedia). The L protein also facilitates essential post-transcriptional modifications, including 5' capping and 3' polyadenylation of viral transcripts, which are necessary for translation by the host cell machinery (UniProt). Because it is vital for the viral life cycle and lacks a direct human counterpart, it is a high-priority target for antiviral drugs (Nature, 2016). Therapeutic approaches include small-molecule inhibitors like remdesivir, which act as chain terminators during RNA synthesis, and RNA interference (RNAi) technologies like TKM-Ebola that specifically target the L polymerase mRNA to block protein production (NIH/PubMed).

Other names
L proteinLarge proteinRNA-dependent RNA polymeraseRdRpEBOV L polymeraseEbola virus L gene
02

Mechanism of action

Inhibition of viral RNA synthesis through nucleoside analog-mediated chain termination and siRNA-mediated degradation of viral mRNA.

03

Biological functions

Viral RNA replicationTranscriptionRNA cappingRNA polyadenylationRNA methylation
04

Disease associations

Infection
05

Safety considerations

HepatotoxicityRenal impairmentInfusion-related reactionsPotential for viral mutational escape and drug resistance
06

Interacting drugs

Remdesivir (GS-5734)

3 more in the full profile.

07

Biomarkers

EBOV RNA viral load (RT-PCR)VP40 antigen levelsSerum alanine aminotransferase (ALT)Serum aspartate aminotransferase (AST)

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