IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-020-20789-7.html
   My bibliography  Save this article

Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape

Author

Listed:
  • Zhiqiang Ku

    (University of Texas Health Science Center at Houston)

  • Xuping Xie

    (University of Texas Medical Branch)

  • Edgar Davidson

    (Integral Molecular, Philadelphia)

  • Xiaohua Ye

    (University of Texas Health Science Center at Houston)

  • Hang Su

    (University of Texas Health Science Center at Houston)

  • Vineet D. Menachery

    (University of Texas Medical Branch)

  • Yize Li

    (University of Pennsylvania)

  • Zihao Yuan

    (University of Texas Health Science Center at Houston)

  • Xianwen Zhang

    (University of Texas Medical Branch)

  • Antonio E. Muruato

    (University of Texas Medical Branch)

  • Ariadna Grinyo i Escuer

    (Integral Molecular, Philadelphia)

  • Breanna Tyrell

    (Integral Molecular, Philadelphia)

  • Kyle Doolan

    (Integral Molecular, Philadelphia)

  • Benjamin J. Doranz

    (Integral Molecular, Philadelphia)

  • Daniel Wrapp

    (University of Texas at Austin)

  • Paul F. Bates

    (University of Pennsylvania)

  • Jason S. McLellan

    (University of Texas at Austin)

  • Susan R. Weiss

    (University of Pennsylvania)

  • Ningyan Zhang

    (University of Texas Health Science Center at Houston)

  • Pei-Yong Shi

    (University of Texas Medical Branch)

  • Zhiqiang An

    (University of Texas Health Science Center at Houston)

Abstract

Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. The determinants for selecting antibody combinations and the mechanism that antibody cocktails prevent viral escape remain unclear. We compared the critical residues in the receptor-binding domain (RBD) used by multiple neutralizing antibodies and cocktails and identified a combination of two antibodies CoV2-06 and CoV2-14 for preventing viral escape. The two antibodies simultaneously bind to non-overlapping epitopes and independently compete for receptor binding. SARS-CoV-2 rapidly escapes from individual antibodies by generating resistant mutations in vitro, but it doesn’t escape from the cocktail due to stronger mutational constraints on RBD-ACE2 interaction and RBD protein folding requirements. We also identified a conserved neutralizing epitope shared between SARS-CoV-2 and SARS-CoV for antibody CoV2-12. Treatments with CoV2-06 and CoV2-14 individually and in combination confer protection in mice. These findings provide insights for rational selection and mechanistic understanding of antibody cocktails as candidates for treating COVID-19.

Suggested Citation

  • Zhiqiang Ku & Xuping Xie & Edgar Davidson & Xiaohua Ye & Hang Su & Vineet D. Menachery & Yize Li & Zihao Yuan & Xianwen Zhang & Antonio E. Muruato & Ariadna Grinyo i Escuer & Breanna Tyrell & Kyle Doo, 2021. "Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20789-7
    DOI: 10.1038/s41467-020-20789-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-20789-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-20789-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Romain Rouet & Jake Y. Henry & Matt D. Johansen & Meghna Sobti & Harikrishnan Balachandran & David B. Langley & Gregory J. Walker & Helen Lenthall & Jennifer Jackson & Stephanie Ubiparipovic & Ohan Ma, 2023. "Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Zhiqiang Ku & Xuping Xie & Jianqing Lin & Peng Gao & Bin Wu & Abbas El Sahili & Hang Su & Yang Liu & Xiaohua Ye & Eddie Yongjun Tan & Xin Li & Xuejun Fan & Boon Chong Goh & Wei Xiong & Hannah Boyd & A, 2022. "Engineering SARS-CoV-2 specific cocktail antibodies into a bispecific format improves neutralizing potency and breadth," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Jing Zou & Hongjie Xia & Xuping Xie & Chaitanya Kurhade & Rafael R. G. Machado & Scott C. Weaver & Ping Ren & Pei-Yong Shi, 2022. "Neutralization against Omicron SARS-CoV-2 from previous non-Omicron infection," Nature Communications, Nature, vol. 13(1), pages 1-4, December.
    4. Yang Liu & Xianwen Zhang & Jianying Liu & Hongjie Xia & Jing Zou & Antonio E. Muruato & Sivakumar Periasamy & Chaitanya Kurhade & Jessica A. Plante & Nathen E. Bopp & Birte Kalveram & Alexander Bukrey, 2022. "A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Sissy Therese Sonnleitner & Martina Prelog & Stefanie Sonnleitner & Eva Hinterbichler & Hannah Halbfurter & Dominik B. C. Kopecky & Giovanni Almanzar & Stephan Koblmüller & Christian Sturmbauer & Leon, 2022. "Cumulative SARS-CoV-2 mutations and corresponding changes in immunity in an immunocompromised patient indicate viral evolution within the host," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Biao Zhou & Runhong Zhou & Bingjie Tang & Jasper Fuk-Woo Chan & Mengxiao Luo & Qiaoli Peng & Shuofeng Yuan & Hang Liu & Bobo Wing-Yee Mok & Bohao Chen & Pui Wang & Vincent Kwok-Man Poon & Hin Chu & Ch, 2022. "A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20789-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.