Norovirus GII.17 major capsid protein VP1 (VP1)

The Norovirus GII.17 major capsid protein VP1 is the primary structural component of the norovirus virion, forming an icosahedral shell that protects the viral RNA genome [1, 3]. It is organized into two main structural domains: the conserved shell (S) domain, which forms the inner core, and the protruding (P) domain, which extends outward and is further divided into P1 and P2 subdomains [1, 16]. The P2 subdomain is highly variable and contains the binding sites for host histo-blood group antigens (HBGAs), which serve as essential attachment factors for viral entry into enterocytes [1, 10]. As the principal target of the host immune response, VP1 is the focus of vaccine development efforts, often utilizing virus-like particles (VLPs) to elicit neutralizing antibodies that block HBGA binding [1, 11, 12]. In addition to its structural role, VP1 has been shown to interact with the viral RNA-dependent RNA polymerase (RdRp) to modulate viral RNA synthesis and requires host chaperones like Hsp90 for its stability and proper folding [2, 15]. Norovirus GII.17 emerged as a major cause of acute gastroenteritis outbreaks worldwide, particularly in Asia during 2014-2015, often displacing the previously dominant GII.4 genotype [9, 13]. Therapeutic strategies targeting VP1 include the development of genotype-specific and multivalent vaccines, as well as monoclonal antibodies designed to neutralize the virus by obstructing its receptor-binding interface [1, 11, 16]. However, the rapid evolution and antigenic drift of the VP1 protein present significant challenges for long-term vaccine efficacy and cross-strain protection [9, 11].

Other names

Major capsid protein VP1Viral protein 1Capsid proteinORF2 protein

Vaccines and monoclonal antibodies target the VP1 protein to induce or provide blockade antibodies that inhibit the interaction between the viral P2 subdomain and host histo-blood group antigens (HBGAs), thereby preventing viral attachment and entry [1, 11, 16]. Small molecule inhibitors of Hsp90 can also lead to the destabilization and degradation of the VP1 protein, inhibiting viral replication [2].