Norwalk virus GI.1 major capsid protein (VP1) (VP1)

The Norwalk virus GI.1 capsid is the icosahedral protein shell of the prototype norovirus strain, which is the leading cause of epidemic acute gastroenteritis worldwide [2, 11]. It is primarily composed of 180 copies of the major structural protein VP1, which self-assembles into a T=3 symmetry structure [7, 9]. The VP1 protein is divided into a conserved shell (S) domain that forms the inner core and a protruding (P) domain that extends from the surface [6, 13]. The P2 subdomain, located at the outermost surface, is the most variable region and contains the binding sites for host histo-blood group antigens (HBGAs), which serve as essential attachment factors for viral entry [6, 14]. Because of its role in host cell recognition and its high immunogenicity, the capsid is a primary target for the development of vaccines, including virus-like particles (VLPs) and viral-vectored platforms [6, 16]. Therapeutic strategies also include the use of monoclonal antibodies and small-molecule glycomimetics designed to block the P2 domain's interaction with HBGAs [6]. However, the rapid antigenic drift of the P2 domain and the high environmental stability of the capsid present significant hurdles for long-term vaccine efficacy and outbreak control [16, 17]. Understanding the dynamic nature of the capsid structure is crucial for designing broad-spectrum inhibitors that can overcome the genetic diversity of norovirus genogroups [17].

Other names

Norwalk virus capsidNorwalk virus GI.1 VP1Major structural protein VP1NV VP1Norwalk virus shell protein

Vaccines such as VXA-NVV-104 and TAK-214 utilize the VP1 protein or virus-like particles (VLPs) to induce neutralizing antibodies and mucosal IgA that block the interaction between the viral P2 domain and host histo-blood group antigens (HBGAs), thereby preventing viral attachment and entry [6, 16]. Experimental monoclonal antibodies like 5B18 and small-molecule glycomimetics also target the P2 domain to competitively inhibit receptor binding and neutralize the virus [6, 17].