Target intelligence / Profile preview

Influenza A virus nucleoprotein (NP) (NP)

Target
NP
Molecular classification
Viral protein, RNA-binding protein, Nucleocapsid protein
01

Overview

Influenza A virus nucleoprotein (NP) is a major structural protein that encapsulates the viral RNA genome, playing a vital role in viral replication, transcription, and the assembly of viral ribonucleoprotein (vRNP) complexes [UniProt: P03466, PMID: 23601558]. Because NP is highly conserved across different influenza A subtypes, its T-cell epitopes are a primary focus for the development of universal influenza vaccines [PMID: 23601558]. These vaccines are designed to stimulate cross-reactive CD8+ and CD4+ T-cell responses, providing heterosubtypic immunity against diverse strains, including seasonal and potential pandemic viruses [ClinicalTrials.gov: NCT03594890, PMID: 27514453]. Beyond vaccines, NP is also a target for small-molecule antivirals that aim to disrupt its oligomerization or interaction with viral RNA, thereby halting the viral life cycle [PMID: 20606667, PMID: 23515124]. The focus on conserved epitopes allows for a broader and more durable immune response compared to traditional vaccines targeting the rapidly mutating surface proteins like hemagglutinin [PMID: 23601558, PMID: 31926806]. Consequently, NP-targeted therapies represent a significant strategy for overcoming the limitations of current influenza prevention and treatment [ClinicalTrials.gov: NCT03594890, PMID: 20606667].

Other names
Nucleocapsid proteinInfluenza A NPNP proteinViral nucleoprotein
02

Mechanism of action

Vaccines targeting conserved NP epitopes induce heterosubtypic T-cell responses (CD4+ and CD8+) to recognize and kill virus-infected cells across different influenza strains [PMID: 23601558, ClinicalTrials.gov: NCT03594890]. Small molecule inhibitors like Nucleozin induce NP aggregation or block its interaction with viral RNA, preventing the formation of functional viral ribonucleoprotein (vRNP) complexes [PMID: 20606667].

03

Biological functions

Viral RNA encapsulationNuclear trafficking of vRNPsViral genome replicationTranscriptionAssembly of viral ribonucleoprotein complexes
04

Disease associations

InfectionInfluenza A infection
05

Safety considerations

Potential for vaccine-associated enhanced respiratory disease (VAERD)Risk of T-cell exhaustionLimited protection against viral entry (non-neutralizing)
06

Interacting drugs

OVX836

6 more in the full profile.

07

Biomarkers

NP-specific CD8+ T-cell countInterferon-gamma (IFN-γ) secretionAnti-NP IgG titers

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