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

Abstract

Antibodies against the receptor-binding-domain 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 anti-spike monoclonal antibodies from COVID-19 patients, and found that some of antibodies against the N-terminal-domain (NTD) induced the open conformation of receptor binding domain (RBD) and thus enhanced the binding capacity of the spike protein to ACE2 and infectivity of SARS-CoV-2. Mutational analysis revealed that all the infectivity-enhancing antibodies recognized a specific site on the NTD. Structural analysis demonstrated that all the 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.

Abstract

A subset antibodies that are detected in patients with severe COVID-19 target a specific region of the N terminal domain of the spike protein and enhance binding of the virus to the ACE2 receptor.