Rabies virus glycoprotein antigenic site III (Site III)

The Rabies virus glycoprotein (RVG) is the primary surface protein of the rabies virus and the sole target for neutralizing antibodies [14, 16]. Antigenic site III is a major, highly conserved conformational epitope located within the ectodomain of the RVG, specifically involving amino acid residues 330 to 338 [11, 18]. This site is critical for the virus's ability to infect host cells, as it facilitates binding to receptors such as the nicotinic acetylcholine receptor (nAChR) and the neural cell adhesion molecule (NCAM) [14, 16]. During the infection process, the glycoprotein undergoes a pH-dependent conformational change from a pre-fusion to a post-fusion state, a transition that site III-specific antibodies can effectively block [2, 12]. Therapeutic monoclonal antibodies, including Foravirumab and Rabivimab, are designed to target this epitope to provide passive immunity in post-exposure prophylaxis (PEP) [4, 11, 18]. By binding to site III, these drugs neutralize the virus and prevent it from entering the central nervous system, where it would otherwise cause a fatal encephalomyelitis [2, 11].

Other names

Antigenic site IIISite IIIRVG Site IIIRabies virus glycoprotein – antigenic epitope IIIRabies virus G protein antigenic site III

Neutralization of viral infectivity by blocking attachment to host receptors or inhibiting pH-dependent conformational changes required for membrane fusion [2, 8, 12].