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TitleAn infectivity-enhancing site on the SARS-CoV-2 spike protein targeted by antibodies.
Journal, issue, pagesCell, Vol. 184, Issue 13, Page 3452-3466.e18, Year 2021
Publish dateJun 24, 2021
AuthorsYafei Liu / Wai Tuck Soh / Jun-Ichi Kishikawa / Mika Hirose / Emi E Nakayama / Songling Li / Miwa Sasai / Tatsuya Suzuki / Asa Tada / Akemi Arakawa / Sumiko Matsuoka / Kanako Akamatsu / Makoto Matsuda / Chikako Ono / Shiho Torii / Kazuki Kishida / Hui Jin / Wataru Nakai / Noriko Arase / Atsushi Nakagawa / Maki Matsumoto / Yukoh Nakazaki / Yasuhiro Shindo / Masako Kohyama / Keisuke Tomii / Koichiro Ohmura / Shiro Ohshima / Toru Okamoto / Masahiro Yamamoto / Hironori Nakagami / Yoshiharu Matsuura / Atsushi Nakagawa / Takayuki Kato / Masato Okada / Daron M Standley / Tatsuo Shioda / Hisashi Arase /
PubMed AbstractAntibodies 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 ...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.
External linksCell / PubMed:34139176 / PubMed Central
MethodsEM (single particle)
Resolution3.45 - 6.08 Å
Structure data

EMDB-30915: Apo spike protein of SARS-CoV2
PDB-7dzw: Apo spike protein from SARS-CoV2
Method: EM (single particle) / Resolution: 3.45 Å

EMDB-30916:
SARS-CoV2 spike protein with Fab fragment of enhancing antibody 8D2
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-30917:
SARS-CoV2 spike protein with Fab fragment of enhancing antibody (8D2)-1
Method: EM (single particle) / Resolution: 3.53 Å

EMDB-30918: SARS-CoV2 spike protein with Fab fragment of enhancing antibody (8D2)-2
PDB-7dzx: Spike protein from SARS-CoV2 with Fab fragment of enhancing antibody 8D2
Method: EM (single particle) / Resolution: 3.82 Å

EMDB-30919:
SARS-CoV2 spike protein with Fab fragment of enhancing antibody (8D2)-3
Method: EM (single particle) / Resolution: 4.16 Å

EMDB-30920:
SARS-CoV2 spike protein with Fab fragment of enhancing antibody (8D2)-4
Method: EM (single particle) / Resolution: 3.74 Å

EMDB-30921: SARS-CoV2 spike protein with Fab fragment of enhancing antibody (2940)-1
PDB-7dzy: Spike protein from SARS-CoV2 with Fab fragment of enhancing antibody 2490
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-30922:
SARS-CoV2 spike protein with Fab fragment of enhancing antibody (2940)-2
Method: EM (single particle) / Resolution: 6.08 Å

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN / SARS-CoV2 / spike protein / Fab / enhancing antibody

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