A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site

Yoshiharu Matsuura, Tomohiro Kurosaki, Tsuyoshi Sekizuka, Noriyo Nagata, Makoto Kuroda, Tadaki Suzuki, Takao Hashiguchi, Yasuhiro Kazuki, Mitsuo Oshimura, Yoshimasa Takahashi, Saya Moriyama, Katsumi Maenaka, Yasuko Orba, Hirofumi Sawa, Akihiko Sato, Takeshi Inoue, Shuhei Sakakibara, Michihito Sasaki, Shuetsu Fukushi, Tateki Suzuki, Jiei Sasaki, Taishi Onodera, Shunsuke Kita, Yu Adachi, Takao Nomura, Takashi Tadokoro, Yuki Anraku, Kohei Yumoto, Cong Tian, Hideo Fukuhara, Nozomi Shiwa, Naoko Iwata, Keisuke Tonouchi, Lin Sun, Hiroyuki Satofuka
2021-08-24

SCID:  54.1/z2ze4w2v
gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.
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2021-08-24
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Authors
Yoshiharu Matsuura
Tomohiro Kurosaki
Tsuyoshi Sekizuka
Noriyo Nagata
Makoto Kuroda
Tadaki Suzuki
Takao Hashiguchi
Yasuhiro Kazuki
Mitsuo Oshimura
Yoshimasa Takahashi
Saya Moriyama
Katsumi Maenaka
Yasuko Orba
Hirofumi Sawa
Akihiko Sato
Takeshi Inoue
Shuhei Sakakibara
Michihito Sasaki
Shuetsu Fukushi
Tateki Suzuki
Jiei Sasaki
Taishi Onodera
Shunsuke Kita
Yu Adachi
Takao Nomura
Takashi Tadokoro
Yuki Anraku
Kohei Yumoto
Cong Tian
Hideo Fukuhara
Nozomi Shiwa
Naoko Iwata
Keisuke Tonouchi
Lin Sun
Hiroyuki Satofuka
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