tetano
Editor, Senior Moderator
Cell
. 2021 May 24;S0092-8674(21)00662-0.
doi: 10.1016/j.cell.2021.05.032. Online ahead of print.
An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies
Yafei Liu[SUP] 1 [/SUP], Wai Tuck Soh[SUP] 2 [/SUP], Jun-Ichi Kishikawa[SUP] 3 [/SUP], Mika Hirose[SUP] 3 [/SUP], Emi E Nakayama[SUP] 4 [/SUP], Songling Li[SUP] 5 [/SUP], Miwa Sasai[SUP] 6 [/SUP], Tatsuya Suzuki[SUP] 7 [/SUP], Asa Tada[SUP] 2 [/SUP], Akemi Arakawa[SUP] 2 [/SUP], Sumiko Matsuoka[SUP] 8 [/SUP], Kanako Akamatsu[SUP] 9 [/SUP], Makoto Matsuda[SUP] 10 [/SUP], Chikako Ono[SUP] 11 [/SUP], Shiho Torii[SUP] 11 [/SUP], Kazuki Kishida[SUP] 2 [/SUP], Hui Jin[SUP] 8 [/SUP], Wataru Nakai[SUP] 1 [/SUP], Noriko Arase[SUP] 12 [/SUP], Atsushi Nakagawa[SUP] 13 [/SUP], Maki Matsumoto[SUP] 14 [/SUP], Yukoh Nakazaki[SUP] 14 [/SUP], Yasuhiro Shindo[SUP] 14 [/SUP], Masako Kohyama[SUP] 1 [/SUP], Keisuke Tomii[SUP] 13 [/SUP], Koichiro Ohmura[SUP] 15 [/SUP], Shiro Ohshima[SUP] 16 [/SUP], Toru Okamoto[SUP] 17 [/SUP], Masahiro Yamamoto[SUP] 18 [/SUP], Hironori Nakagami[SUP] 19 [/SUP], Yoshiharu Matsuura[SUP] 20 [/SUP], Atsushi Nakagawa[SUP] 21 [/SUP], Takayuki Kato[SUP] 3 [/SUP], Masato Okada[SUP] 22 [/SUP], Daron M Standley[SUP] 23 [/SUP], Tatsuo Shioda[SUP] 24 [/SUP], Hisashi Arase[SUP] 25 [/SUP]
Affiliations
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.
Keywords: ADE; angiotensin converting enzyme 2; antibody-dependent enhancement; cryo-EM; cryo-electron microscopy; docking model.
. 2021 May 24;S0092-8674(21)00662-0.
doi: 10.1016/j.cell.2021.05.032. Online ahead of print.
An infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies
Yafei Liu[SUP] 1 [/SUP], Wai Tuck Soh[SUP] 2 [/SUP], Jun-Ichi Kishikawa[SUP] 3 [/SUP], Mika Hirose[SUP] 3 [/SUP], Emi E Nakayama[SUP] 4 [/SUP], Songling Li[SUP] 5 [/SUP], Miwa Sasai[SUP] 6 [/SUP], Tatsuya Suzuki[SUP] 7 [/SUP], Asa Tada[SUP] 2 [/SUP], Akemi Arakawa[SUP] 2 [/SUP], Sumiko Matsuoka[SUP] 8 [/SUP], Kanako Akamatsu[SUP] 9 [/SUP], Makoto Matsuda[SUP] 10 [/SUP], Chikako Ono[SUP] 11 [/SUP], Shiho Torii[SUP] 11 [/SUP], Kazuki Kishida[SUP] 2 [/SUP], Hui Jin[SUP] 8 [/SUP], Wataru Nakai[SUP] 1 [/SUP], Noriko Arase[SUP] 12 [/SUP], Atsushi Nakagawa[SUP] 13 [/SUP], Maki Matsumoto[SUP] 14 [/SUP], Yukoh Nakazaki[SUP] 14 [/SUP], Yasuhiro Shindo[SUP] 14 [/SUP], Masako Kohyama[SUP] 1 [/SUP], Keisuke Tomii[SUP] 13 [/SUP], Koichiro Ohmura[SUP] 15 [/SUP], Shiro Ohshima[SUP] 16 [/SUP], Toru Okamoto[SUP] 17 [/SUP], Masahiro Yamamoto[SUP] 18 [/SUP], Hironori Nakagami[SUP] 19 [/SUP], Yoshiharu Matsuura[SUP] 20 [/SUP], Atsushi Nakagawa[SUP] 21 [/SUP], Takayuki Kato[SUP] 3 [/SUP], Masato Okada[SUP] 22 [/SUP], Daron M Standley[SUP] 23 [/SUP], Tatsuo Shioda[SUP] 24 [/SUP], Hisashi Arase[SUP] 25 [/SUP]
Affiliations
- PMID: 34139176
- DOI: 10.1016/j.cell.2021.05.032
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.
Keywords: ADE; angiotensin converting enzyme 2; antibody-dependent enhancement; cryo-EM; cryo-electron microscopy; docking model.