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


ABSTRACT: 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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC8142859 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Liu Yafei Y   Soh Wai Tuck WT   Kishikawa Jun-Ichi JI   Hirose Mika M   Nakayama Emi E EE   Li Songling S   Sasai Miwa M   Suzuki Tatsuya T   Tada Asa A   Arakawa Akemi A   Matsuoka Sumiko S   Akamatsu Kanako K   Matsuda Makoto M   Ono Chikako C   Torii Shiho S   Kishida Kazuki K   Jin Hui H   Nakai Wataru W   Arase Noriko N   Nakagawa Atsushi A   Matsumoto Maki M   Nakazaki Yukoh Y   Shindo Yasuhiro Y   Kohyama Masako M   Tomii Keisuke K   Ohmura Koichiro K   Ohshima Shiro S   Okamoto Toru T   Yamamoto Masahiro M   Nakagami Hironori H   Matsuura Yoshiharu Y   Nakagawa Atsushi A   Kato Takayuki T   Okada Masato M   Standley Daron M DM   Shioda Tatsuo T   Arase Hisashi H  

Cell 20210524 13


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 i  ...[more]

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