An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies

Yafei Liu,Wai Tuck Soh,Jun-Ichi Kishikawa,et al.

Antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein prevent SARS-CoV-2 infection.However,the effects of antibodies against other spike protein domains are largely unknown.Here,we screened a series of antispike monoclonal antibodies from coronavirus disease 2019 (COVID-19) patients and found that some of antibodies against the N-terminal domain (NTD) induced the open conformation of RBD and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2.Mutational analysis revealed that all of the infectivity-enhancing antibodies recognized a specific site on the NTD.Structural analysis demonstrated that all infectivity-enhancing antibodies bound to NTD in a similar manner.The antibodies against this infectivity-enhancing site were detected at high levels in severe patients.Moreover,we identified antibodies against the infectivity-enhancing site in uninfected donors,albeit at a lower frequency.These findings demonstrate that not only neutralizing antibodies but also enhancing antibodies are produced during SARS-CoV-2 infection.