Target intelligence / Profile preview

Norovirus GI.4 major capsid protein VP1 (GI.4 VP1) (GI.4 VP1)

Target
GI.4 VP1
Molecular classification
Viral protein, Capsid protein, Structural protein
01

Overview

The Norovirus GI.4 VP1 capsid protein is the primary structural component of the Genogroup I, Genotype 4 norovirus, which is a significant cause of acute gastroenteritis in humans. This protein self-assembles into an icosahedral capsid, typically consisting of 180 copies (T=3 symmetry), which serves to protect the viral RNA genome and mediate infection by binding to host cell receptors. The VP1 protein is divided into a conserved shell (S) domain and a protruding (P) domain; the P domain is further subdivided into P1 and P2 subdomains, with P2 being the most surface-exposed region and the primary site for interaction with host histo-blood group antigens (HBGAs). GI.4 strains, such as the Chiba strain, are important targets for vaccine development and have been explored in bivalent vaccine formulations alongside GII.4 strains. Therapeutic strategies targeting this protein include virus-like particle (VLP) vaccines and neutralizing monoclonal antibodies, such as CV-1A1 and CV-2F5, which function by blocking viral attachment or disrupting the capsid structure. A notable challenge in utilizing GI.4 VP1 as a therapeutic target is its relative structural instability compared to GII.4 variants, which can complicate the production and formulation of VLP-based vaccines.

Other names
Major capsid protein VP1ORF2 proteinCapsid protein VP1Chiba virus capsid protein
02

Mechanism of action

Neutralization of viral infectivity by blocking attachment to host cell receptors (HBGAs) or inducing capsid disruption.

03

Biological functions

Viral attachmentViral entryCapsid assemblyHost cell recognitionHisto-blood group antigen (HBGA) binding
04

Disease associations

InfectionGastroenteritis
05

Safety considerations

Antigenic driftStrain-specific immunityStructural instability of GI.4 VLPs compared to GII.4Potential for immune escape
06

Interacting drugs

Bivalent norovirus VLP vaccine candidate (GI.4/GII.4)

2 more in the full profile.

07

Biomarkers

Anti-GI.4 VP1 antibodiesGI.4 viral RNAGI.4 capsid antigen

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