Immunity · 2021
A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Onodera Taishi, Kita Shunsuke, Adachi Yu, Moriyama Saya, Sato Akihiko, Nomura Takao, Sakakibara Shuhei, Inoue Takeshi, Tadokoro Takashi, Anraku Yuki, Yumoto Kohei, Tian Cong, Fukuhara Hideo, Sasaki Michihito, Orba Yasuko, Shiwa Nozomi, Iwata Naoko, Nagata Noriyo, Suzuki Tateki, Sasaki Jiei, Sekizuka Tsuyoshi, Tonouchi Keisuke, Sun Lin, Fukushi Shuetsu, Satofuka Hiroyuki, Kazuki Yasuhiro, Oshimura Mitsuo, Kurosaki Tomohiro, Kuroda Makoto, Matsuura Yoshiharu, Suzuki Tadaki, Sawa Hirofumi, Hashiguchi Takao, Maenaka Katsumi, Takahashi Yoshimasa
Аннотация
Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH 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.