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

Cell

Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, Osaka University, Osaka 565-0871, Japan. Electronic address:

Published: June 2021

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 anti-spike 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142859PMC
http://dx.doi.org/10.1016/j.cell.2021.05.032DOI Listing

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