Viral suppression function of intracellular antibody against C-terminal domain of rabies virus phosphoprotein

Rabies virus (RV) causes afatal disease in both human and animals. The disease can be prevented by post-exposure prophylaxis in individuals exposed to RV. However, the neutralization effect is limited afterthe virusenters into the host cells.So, itisimportant toidentifynew targetsforrabiestherapy. In this study, a human antibody RV1A2 specific to RV phosphoprotein (RV-P) was generated from a human naive immune antibody library. The antibody recognized all forms of the phosphoproteins including the full length (P1) and short length of the P proteins (P2, P3, P4, and P5). The epitope mapping and the molecular docking of antigen–antibody complex showed that the antibody targets at a conserved epitope of ‘VLGWV’ ranging from amino acid (aa) 262 to 266 at C-terminal domain of the P protein, which locates at a hydrophobic pocket region in the C-terminal of the RV-P. The aa W265 within the epitope is on the flat surface of the domain, suggesting that it may be a critical amino acid for the functions of the P protein. Our results further showed that intracellular antibody RV1A2 which targets at the C-terminal domain of the P protein could effectively inhibit RV propagation 2–4 days post infection. These results suggest that the conserved C-terminal domain may be used as a new target for drug discovery, which highlights an intracellular inhibition of RV propagation and provides a potential novel way to treat RV infection.