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Cited by 22SARS-CoV-2 and COVID-19 Researchvaccines and immunoinformatics approachesMonoclonal and Polyclonal Antibodies Research

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Structural delineation and computational design of SARS-CoV-2-neutralizing antibodies against Omicron subvariants

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Moriyama, Saya, Anraku, Yuki, Taminishi, Shunta, Adachi, Yu, Kuroda, Daisuke, Kita, Shunsuke, Higuchi, Yusuke, Kirita, Yuhei, Kotaki, Ryutaro, Tonouchi, Keisuke, Yumoto, Kohei, Suzuki, Tateki, Someya, Taiyou, Fukuhara, Hideo, Kuroda, Yudai, Yamamoto, Tsukasa, Onodera, Taishi, Fukushi, Shuetsu, Maeda, Ken, Nakamura-Uchiyama, Fukumi, Hashiguchi, Takao, Hoshino, Atsushi, Maenaka, Katsumi, Takahashi, Yoshimasa·2023·Nature Communications
DOI 10.1038/s41467-023-39890-8PMC PMC10349087

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Abstract

SARS-CoV-2 Omicron subvariants have evolved to evade receptor-binding site (RBS) antibodies that exist in diverse individuals as public antibody clones. We rationally selected RBS antibodies resilient to mutations in emerging Omicron subvariants. Y489 was identified as a site of virus vulnerability and a common footprint of broadly neutralizing antibodies against the subvariants. Multiple Y489-binding antibodies were encoded by public clonotypes and additionally recognized F486, potentially accounting for the emergence of Omicron subvariants harboring the F486V mutation. However, a subclass of antibodies broadly neutralized BA.4/BA.5 variants via hydrophobic binding sites of rare clonotypes along with high mutation-resilience under escape mutation screening. A computationally designed antibody based on one of the Y489-binding antibodies, NIV-10/FD03, was able to bind XBB with any 486 mutation and neutralized XBB.1.5. The structural basis for the mutation-resilience of this Y489-binding antibody group may provide important insights into the design of therapeutics resistant to viral escape.

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Metadata

Authors
Moriyama, S., Anraku, Y., Taminishi, S., Adachi, Y., Kuroda, D., Kita, S., Higuchi, Y., Kirita, Y., Kotaki, R., Tonouchi, K., Yumoto, K., Suzuki, T., Someya, T., Fukuhara, H., Kuroda, Y., Yamamoto, T., Onodera, T., Fukushi, S., Maeda, K., Nakamura-Uchiyama, F., Hashiguchi, T., Hoshino, A., Maenaka, K., & Takahashi, Y.
Affiliations
  • National Institute of Infectious Diseases (JP)
  • Hokkaido University (JP)
  • Kyoto Prefectural University of Medicine (JP)
  • Waseda University (JP)
  • Kyoto University (JP)
Corresponding author
  • Moriyama, Saya
  • Takahashi, Yoshimasa
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-07-14
Volume
14
Issue
1
Pages
4198-4198
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-39890-8
PMC
PMC10349087
OpenAlex
W4384298552
Cited by
22
References
8
Citations by year
2026: 3 · 2025: 7 · 2024: 9 · 2023: 3
FWCI
4.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Japan Agency for Medical Research and Development (JP20fk0108516, JP22wm0325047, JP20fk0108298, JP223fa627009, JP21fk0108465, JP20fk0108534, JP21fk0108534, JP22ama121037, JP223fa627005, JP22gm1810004, JP19fk0108104, JP20fk0108104, JP22fk0108141)
  • MEXT | Japan Society for the Promotion of Science (JP19H04202, JP20H05773, JP20H05873)
  • MEXT | JST | Core Research for Evolutional Science and Technology (JPMJCR20H8)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
Keywords
SARS-CoV-2 Omicron subvariants, neutralizing antibodies, receptor binding sites, XBB.1.5, BA.4/BA.5, antibody escape mutations, antibody design, hydrophobic binding site
MeSH terms
Broadly Neutralizing Antibodies, COVID-19, SARS-CoV-2, Antibodies, Viral, Binding Sites, Humans, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus

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