3.2  CoV S-RBD-specific neutralizing antibodies
So far, most neutralizing antibodies recognize the RBD in the S protein S2 of CoVs. Compared with the high mutation rate in the S1 protein, S2 is much more conservative, thereby decreasing the off-target risk caused by amino acid replacement [62], and also bypassing the special epitopes that may cause ADE [63]. This means that the cocktail of monoclonal antibodies binding to different epitopes of RBD would be more desirable for therapeutic purposes [64]. For treatment, the monoclonal antibodies are from a human source or are humanized antibodies, isolated or generated with various approaches. For example, wild-type mice were immunized with soluble recombinant RBD containing the S protein. Then mouse antibodies were humanized and isolated, or transgenic mice were directly immunized, to express human versions of the antibodies [50,65,66]. However, direct cloning of single B cells from human survivors, used in combination with the phage-display antibody library, could provide authentic human antibodies. Until now, it should be noted that many neutralizing antibodies have been successfully discovered for treatment of SARS-CoV [67] and MERS-CoV infection [45,68,69]. These antibodies have all been described favorably in the literature [29,70,71]. A similar approach is known as single chain fragment variable (scFv) library screening, whereby the use of RBD as a bait protein allows some neutralizing antibodies to be screened out from non-immune humans [72,73].
Antibodies effective at inhibiting SARS-CoV infection should also have the potential for treatment of 2019-nCoV as well, as long as the binding motif in RBD shares the same sequences. The new neutralizing monoclonal antibodies would also be isolated from the patients using the established techniques.