Human metapneumovirus RNA-directed RNA polymerase (HMPV RdRp) (HMPV RdRp)

The Human metapneumovirus (HMPV) RNA-directed RNA polymerase (RdRp) is a complex enzymatic machine, primarily composed of the Large (L) protein, that is essential for the viral life cycle. It functions as the catalytic core of the viral replication complex, responsible for both the replication of the negative-sense RNA genome and the transcription of viral messenger RNAs (UniProt: Q6WB93). The enzyme also possesses activities for 5' capping and 3' polyadenylation of viral transcripts, making it a versatile target for antiviral intervention (PubMed: 32251630). Because HMPV is a significant cause of severe respiratory disease in vulnerable populations, including infants and the elderly, the RdRp is a focal point for drug development. Nucleoside analogs like remdesivir and lumicitabine target this polymerase by mimicking natural nucleotides, leading to the termination of RNA chain elongation or the introduction of lethal mutations into the viral genome (PubMed: 25691586). Despite its potential, challenges remain in achieving high selectivity over host polymerases and managing the potential for rapid viral evolution and resistance.

Other names

Large structural proteinL proteinRNA-directed RNA polymeraseHMPV L proteinRNA-dependent RNA polymerase

Inhibition of viral RNA synthesis through competitive substrate binding and premature chain termination.