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

[tetano]

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 ¹ , Wai Tuck Soh ² , Jun-Ichi Kishikawa ³ , Mika Hirose ³ , Emi E Nakayama ⁴ , Songling Li ⁵ , Miwa Sasai ⁶ , Tatsuya Suzuki ⁷ , Asa Tada ² , Akemi Arakawa ² , Sumiko Matsuoka ⁸ , Kanako Akamatsu ⁹ , Makoto Matsuda ¹⁰ , Chikako Ono ¹¹ , Shiho Torii ¹¹ , Kazuki Kishida ² , Hui Jin ⁸ , Wataru Nakai ¹ , Noriko Arase ¹² , Atsushi Nakagawa ¹³ , Maki Matsumoto ¹⁴ , Yukoh Nakazaki ¹⁴ , Yasuhiro Shindo ¹⁴ , Masako Kohyama ¹ , Keisuke Tomii ¹³ , Koichiro Ohmura ¹⁵ , Shiro Ohshima ¹⁶ , Toru Okamoto ¹⁷ , Masahiro Yamamoto ¹⁸ , Hironori Nakagami ¹⁹ , Yoshiharu Matsuura ²⁰ , Atsushi Nakagawa ²¹ , Takayuki Kato ³ , Masato Okada ²² , Daron M Standley ²³ , Tatsuo Shioda ²⁴ , Hisashi Arase ²⁵



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.