Rabies virus glycoprotein (RABV-G) (RABV-G)

The Rabies virus glycoprotein (RABV-G) is the sole protein exposed on the surface of the rabies virus envelope and is the primary target for neutralizing antibodies [UniProt]. It is a type I transmembrane glycoprotein that assembles into trimeric spikes, which are essential for viral attachment to host cell receptors such as the nicotinic acetylcholine receptor (nAChR) and neural cell adhesion molecule (NCAM) [PubMed]. Antigenic site II is a major, discontinuous conformational epitope on the glycoprotein that is highly conserved and targeted by many potent neutralizing monoclonal antibodies [PubMed]. In clinical practice, therapies targeting this site, including rabies immunoglobulins and monoclonal antibodies like Rabivimab, are administered as part of post-exposure prophylaxis (PEP) to neutralize the virus at the site of entry before it can infect the nervous system [WHO]. Because rabies is almost invariably fatal once it reaches the central nervous system, the glycoprotein's role in mediating viral entry makes it the most critical target for both passive immunization and vaccine development [NIH]. Drugs binding to site II typically function by sterically hindering receptor interactions or by preventing the structural rearrangements necessary for pH-dependent membrane fusion [PubMed]. The structural integrity of site II is a key consideration in the design of recombinant vaccines and the selection of monoclonal antibody cocktails to prevent viral escape [PubMed].

Other names

Rabies virus G proteinRabies virus surface glycoproteinAntigenic site II of rabies virus glycoproteinRABV G

Neutralization of viral infectivity by blocking receptor binding or preventing the conformational change required for membrane fusion.