Norovirus GII.4 major capsid protein VP1 protruding domain (VP1 P domain) (VP1 P domain)

The protruding (P) domain of the Norovirus GII.4 major capsid protein VP1 is a critical structural component of the viral capsid that mediates host cell attachment and entry (Prasad et al., 1999; UniProt A0A172QPU7). It is divided into two subdomains, P1 and P2, with the P2 subdomain being the most surface-exposed and hypervariable region of the virus (Tan et al., 2008). This domain contains the binding sites for histo-blood group antigens (HBGAs), which act as essential attachment factors or co-receptors for norovirus infection (Hutson et al., 2002). Because of its accessibility and role in receptor binding, the P domain is the primary target for neutralizing antibodies and the focus of vaccine development efforts, including virus-like particle (VLP) and P-particle candidates (Takeda/HilleVax TAK-214; Vaxart VXA-NVV-104). However, the GII.4 genotype is characterized by rapid antigenic drift within the P domain, allowing the virus to escape host herd immunity and cause periodic global pandemics of acute gastroenteritis (Lindesmith et al., 2008). Therapeutic strategies targeting this domain include VLP-based vaccines and experimental monoclonal antibodies designed to block HBGA interactions (Ford-Siltz et al., 2020).

Other names

P domainProtruding domainVP1 P-domainP1 subdomainP2 subdomainCapsid protein P domain

Inhibition of viral attachment to host histo-blood group antigens (HBGAs) and neutralization of the virus by blocking the P2 subdomain binding interface.