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A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses.

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Wang P, Casner RG, Nair MS, Yu J, Guo Y, Wang M, Chan JF, Cerutti G, Iketani S, Liu L, Sheng Z, Chen Z, Yuen KY, Kwong PD, Huang Y, Shapiro L, Ho DD
OpenAccess logo Emerg Microbes Infect 11 147-157 (2022)
Cited: 21 times
EuropePMC logo PMID: 34836485

Abstract

The repeated emergence of highly pathogenic human coronaviruses as well as their evolving variants highlight the need to develop potent and broad-spectrum antiviral therapeutics and vaccines. By screening monoclonal antibodies (mAbs) isolated from COVID-19-convalescent patients, we found one mAb, 2-36, with cross-neutralizing activity against SARS-CoV. We solved the cryo-EM structure of 2-36 in complex with SARS-CoV-2 or SARS-CoV spike, revealing a highly conserved epitope in the receptor-binding domain (RBD). Antibody 2-36 neutralized not only all current circulating SARS-CoV-2 variants and SARS-COV, but also a panel of bat and pangolin sarbecoviruses that can use human angiotensin-converting enzyme 2 (ACE2) as a receptor. We selected 2-36-escape viruses in vitro and confirmed that K378 T in SARS-CoV-2 RBD led to viral resistance. Taken together, 2-36 represents a strategic reserve drug candidate for the prevention and treatment of possible diseases caused by pre-emergent SARS-related coronaviruses. Its epitope defines a promising target for the development of a pan-sarbecovirus vaccine.

Articles - 7n5h mentioned but not cited (3)

  1. A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses. Wang P, Casner RG, Nair MS, Yu J, Guo Y, Wang M, Chan JF, Cerutti G, Iketani S, Liu L, Sheng Z, Chen Z, Yuen KY, Kwong PD, Huang Y, Shapiro L, Ho DD. Emerg Microbes Infect 11 147-157 (2022)
  2. research-article A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses. Wang P, Casner RG, Nair MS, Yu J, Guo Y, Wang M, Chan JF, Cerutti G, Iketani S, Liu L, Sheng Z, Chen Z, Yuen KY, Kwong PD, Huang Y, Shapiro L, Ho DD. bioRxiv 2021.10.13.464307 (2021)
  3. Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants. Chi X, Xia L, Zhang G, Chi X, Huang B, Zhang Y, Chen Z, Han J, Wu L, Li Z, Sun H, Huang P, Yu C, Chen W, Zhou Q. Cell Discov 9 37 (2023)


Reviews citing this publication (7)

  1. Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses. Chen Y, Zhao X, Zhou H, Zhu H, Jiang S, Wang P. Nat Rev Immunol 23 189-199 (2023)
  2. Protective neutralizing epitopes in SARS-CoV-2. Liu H, Wilson IA. Immunol Rev 310 76-92 (2022)
  3. SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies. Cox M, Peacock TP, Harvey WT, Hughes J, Wright DW, COVID-19 Genomics UK (COG-UK) Consortium, Willett BJ, Thomson E, Gupta RK, Peacock SJ, Robertson DL, Carabelli AM. Nat Rev Microbiol 21 112-124 (2023)
  4. Human Coronavirus Cell Receptors Provide Challenging Therapeutic Targets. López-Cortés GI, Palacios-Pérez M, Hernández-Aguilar MM, Veledíaz HF, José MV. Vaccines (Basel) 11 174 (2023)
  5. Protective and pathogenic role of humoral responses in COVID-19. Park U, Cho NH. J Microbiol 60 268-275 (2022)
  6. State of the art in epitope mapping and opportunities in COVID-19. Hamed SM, Sakr MM, El-Housseiny GS, Wasfi R, Aboshanab KM. Future Sci OA 16 FSO832 (2023)
  7. Therapeutic antibodies for COVID-19: is a new age of IgM, IgA and bispecific antibodies coming? Zhang J, Zhang H, Sun L. MAbs 14 2031483 (2022)

Articles citing this publication (11)

  1. Antibody evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2, and BA.3 sub-lineages. Ai J, Wang X, He X, Zhao X, Zhang Y, Jiang Y, Li M, Cui Y, Chen Y, Qiao R, Li L, Yang L, Li Y, Hu Z, Zhang W, Wang P. Cell Host Microbe 30 1077-1083.e4 (2022)
  2. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Gruell H, Vanshylla K, Tober-Lau P, Hillus D, Schommers P, Lehmann C, Kurth F, Sander LE, Klein F. Nat Med 28 477-480 (2022)
  3. An antibody class with a common CDRH3 motif broadly neutralizes sarbecoviruses. Liu L, Iketani S, Guo Y, Reddem ER, Casner RG, Nair MS, Yu J, Chan JF, Wang M, Cerutti G, Li Z, Morano NC, Castagna CD, Corredor L, Chu H, Yuan S, Poon VK, Chan CC, Chen Z, Luo Y, Cunningham M, Chavez A, Yin MT, Perlin DS, Tsuji M, Yuen KY, Kwong PD, Sheng Z, Huang Y, Shapiro L, Ho DD. Sci Transl Med 14 eabn6859 (2022)
  4. Inter-domain communication in SARS-CoV-2 spike proteins controls protease-triggered cell entry. Qing E, Li P, Cooper L, Schulz S, Jäck HM, Rong L, Perlman S, Gallagher T. Cell Rep 39 110786 (2022)
  5. Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies. Wang X, Zhao X, Song J, Wu J, Zhu Y, Li M, Cui Y, Chen Y, Yang L, Liu J, Zhu H, Jiang S, Wang P. Emerg Microbes Infect 11 477-481 (2022)
  6. Human antibodies to SARS-CoV-2 with a recurring YYDRxG motif retain binding and neutralization to variants of concern including Omicron. Liu H, Kaku CI, Song G, Yuan M, Andrabi R, Burton DR, Walker LM, Wilson IA. Commun Biol 5 766 (2022)
  7. Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19 : A Cohort Study. Kip KE, McCreary EK, Collins K, Minnier TE, Snyder GM, Garrard W, McKibben JC, Yealy DM, Seymour CW, Huang DT, Bariola JR, Schmidhofer M, Wadas RJ, Angus DC, Kip PL, Marroquin OC. Ann Intern Med 176 496-504 (2023)
  8. Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking. Liu L, Casner RG, Guo Y, Wang Q, Iketani S, Chan JF, Yu J, Dadonaite B, Nair MS, Mohri H, Reddem ER, Yuan S, Poon VK, Chan CC, Yuen KY, Sheng Z, Huang Y, Bloom JD, Shapiro L, Ho DD. Immunity 56 2442-2455.e8 (2023)
  9. Broad Sarbecovirus Neutralizing Antibodies Obtained by Computational Design and Synthetic Library Screening. Yang X, Duan H, Liu X, Zhang X, Pan S, Zhang F, Gao P, Liu B, Yang J, Chi X, Yang W. J Virol 97 e0061023 (2023)
  10. Machine Learning Classification of Time since BNT162b2 COVID-19 Vaccination Based on Array-Measured Antibody Activity. Ma QL, Huang FM, Guo W, Feng KY, Huang T, Cai YD. Life (Basel) 13 1304 (2023)
  11. Tixagevimab/Cilgavimab as pre-exposure prophylaxis against SARS-CoV-2 in patients with hematological malignancies. Angotzi F, Petrella M, Berno T, Binotto G, Bonetto G, Branca A, Carraro M, Cavaretta CA, Cellini A, D'Amore F, Forlani L, Gianesello I, Gurrieri C, Imbergamo S, Lessi F, Maroccia A, Mazzetto F, Pavan L, Pezone S, Piazza F, Pravato S, Ruocco V, Scapinello G, Vianello F, Zambello R, Zatta I, Zoletto S, Padoan A, Trentin L, Visentin A. Front Oncol 13 1212752 (2023)


Related citations provided by authors (1)

  1. A monoclonal antibody that neutralizes SARS-CoV-2 variants, SARS-CoV, and other sarbecoviruses.. Wang P, Casner RG, Nair MS, Yu J, Guo Y, Wang M, Chan JF, Cerutti G, Iketani S, Liu L, Sheng Z, Chen Z, Yuen KY, Kwong PD, Huang Y, Shapiro L, Ho DD bioRxiv (2021)

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