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

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

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.