Structural and virological identification of neutralizing antibody footprint provides insights into therapeutic antibody design against SARS-CoV-2 variants
Abstrak
Abstract Medical treatments using potent neutralizing SARS-CoV-2 antibodies have achieved remarkable improvements in clinical symptoms, changing the situation for the severity of COVID-19 patients. We previously reported an antibody, NT-108 with potent neutralizing activity. However, the structural and functional basis for the neutralizing activity of NT-108 has not yet been understood. Here, we demonstrated the therapeutic effects of NT-108 in a hamster model and its protective effects at low doses. Furthermore, we determined the cryo-EM structure of NT-108 in complex with SARS-CoV-2 spike. The single-chain Fv construction of NT-108 improved the cryo-EM maps because of the prevention of preferred orientations induced by Fab orientation. The footprints of NT-108 illuminated how escape mutations such as E484K evade from class 2 antibody recognition without ACE2 affinity attenuation. The functional and structural basis for the potent neutralizing activity of NT-108 provides insights into the rational design of therapeutic antibodies.
Topik & Kata Kunci
Penulis (25)
Yuki Anraku
Shunsuke Kita
Taishi Onodera
Akihiko Sato
Takashi Tadokoro
Shiori Ito
Yu Adachi
Ryutaro Kotaki
Tateki Suzuki
Jiei Sasaki
Nozomi Shiwa-Sudo
Naoko Iwata-Yoshikawa
Noriyo Nagata
Souta Kobayashi
Yasuhiro Kazuki
Mitsuo Oshimura
Takao Nomura
Michihito Sasaki
Yasuko Orba
Tadaki Suzuki
Hirofumi Sawa
Takao Hashiguchi
Hideo Fukuhara
Yoshimasa Takahashi
Katsumi Maenaka
Format Sitasi
Akses Cepat
- Tahun Terbit
- 2025
- Sumber Database
- DOAJ
- DOI
- 10.1038/s42003-025-07827-0
- Akses
- Open Access ✓