Rational in silico design identifies two mutations that restore UT28K SARS-CoV-2 monoclonal antibody activity against Omicron BA.1.

SARS-CoV-2 in silico designed neutralizing antibodies

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
05 Jan 2024
Historique:
received: 07 09 2023
revised: 27 11 2023
accepted: 20 12 2023
medline: 17 1 2024
pubmed: 17 1 2024
entrez: 16 1 2024
Statut: aheadofprint

Résumé

SARS-CoV-2 rapidly mutates and acquires resistance to neutralizing antibodies. We report an in-silico-designed antibody that restores the neutralizing activity of a neutralizing antibody. Our previously generated antibody, UT28K, exhibited broad neutralizing activity against mutant variants; however, its efficacy against Omicron BA.1 was compromised by the mutation. Using previously determined structural information, we designed a modified-UT28K (V

Identifiants

DOI: 10.1016/j.str.2023.12.013 PMID: 38228146
pubmed: 38228146
pii: S0969-2126(23)00454-9
doi: 10.1016/j.str.2023.12.013
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests T.O., H.K., H.N., and H.T. have patent applications pending UT28K (JP2021-056423). T.O., H.T., Y.I., and T.H. have patent applications pending UT28K-RD (JP2022-149604).

Auteurs

Tatsuhiko Ozawa (T)

Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan; Center for Advanced Antibody Drug Development, University of Toyama, Toyama, Japan. Electronic address: toz@med.u-toyama.ac.jp.

Yoshiki Ikeda (Y)

Institute for Integrated Cell-Material Sciences, Kyoto University, Yoshidahonnmachi, Sakyo-ku, Kyoto, Japan. Electronic address: ikeda.yoshiki.3r@kyoto-u.ac.jp.

Liuan Chen (L)

Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

Rigel Suzuki (R)

Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan.

Atsushi Hoshino (A)

Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Akira Noguchi (A)

Department of Diagnostic Pathology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.

Shunsuke Kita (S)

Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

Yuki Anraku (Y)

Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.

Emiko Igarashi (E)

Department of Virology, Toyama Institute of Health, Toyama, Japan.

Yumiko Saga (Y)

Department of Virology, Toyama Institute of Health, Toyama, Japan.

Noriko Inasaki (N)

Department of Virology, Toyama Institute of Health, Toyama, Japan.

Shunta Taminishi (S)

Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Jiei Sasaki (J)

Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.

Yuhei Kirita (Y)

Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Hideo Fukuhara (H)

Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Division of Pathogen Structure, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.

Katsumi Maenaka (K)

Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Division of Pathogen Structure, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan; Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Sapporo, Japan.

Takao Hashiguchi (T)

Laboratory of Medical Virology, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan.

Takasuke Fukuhara (T)

Department of Microbiology and Immunology, Faculty of Medicine, Hokkaido University, Sapporo, Japan; Institute for Vaccine Research and Development (HU-IVReD), Hokkaido University, Sapporo, Japan; Laboratory of Virus Control, Research Institute for Microbial Diseases, Osaka University, Suita, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.

Kenichi Hirabayashi (K)

Department of Diagnostic Pathology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.

Hideki Tani (H)

Department of Virology, Toyama Institute of Health, Toyama, Japan.

Hiroyuki Kishi (H)

Department of Immunology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan; Center for Advanced Antibody Drug Development, University of Toyama, Toyama, Japan.

Hideki Niimi (H)

Center for Advanced Antibody Drug Development, University of Toyama, Toyama, Japan; Department of Clinical Laboratory and Molecular Pathology, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama, Japan.

Classifications MeSH