Target intelligence / Profile preview

Influenza A virus non-structural protein 1 (NS1) (NS1)

Target
NS1
Molecular classification
Viral protein, RNA-binding protein, Interferon antagonist, Transcription factor regulator
01

Overview

Influenza A virus non-structural protein 1 (NS1) is a primary virulence factor and a multifunctional protein essential for the virus to overcome host innate immunity. Its most prominent role is acting as an interferon (IFN) antagonist, where it suppresses the production of IFN-alpha/beta by interacting with RIG-I and inhibiting the processing of host cellular pre-mRNAs through binding to CPSF30 (UniProt P03496; PMID: 22532081). NS1 also binds double-stranded RNA (dsRNA), sequestering it from host sensors that would otherwise trigger an antiviral state. In addition to immune evasion, NS1 modulates viral replication and host cell signaling pathways, such as the PI3K/Akt pathway, to favor viral survival (PMID: 29437906). While no FDA-approved drugs currently target NS1, it is a major focus of antiviral research because its inhibition allows the host's natural immune system to effectively combat the infection. Experimental small molecules aim to disrupt its RNA-binding domain or its interaction with host proteins to restore the immune response (PMID: 30108117).

Other names
Non-structural protein 1NS1ANS1 proteinInfluenza A virus NS1
02

Mechanism of action

Inhibition of NS1-mediated suppression of the host antiviral response, specifically by blocking its interaction with CPSF30 or RIG-I, or preventing its binding to double-stranded RNA.

03

Biological functions

Immune response evasionInterferon antagonismRNA bindingInhibition of host mRNA processingRegulation of viral replicationPI3K signaling activation
04

Disease associations

InfectionInfluenza A
05

Safety considerations

High genetic variability among influenza strainsPotential for rapid emergence of drug resistanceTargeting a protein with multiple host-protein interactions may lead to off-target effects
06

Interacting drugs

JJ3297

3 more in the full profile.

07

Biomarkers

Viral RNA loadInterferon-beta expression levelsNS1 protein concentration

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