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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
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    Citations

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    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.

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