N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2

  1. Fang Tian
  2. Bei Tong  Is a corresponding author
  3. Liang Sun
  4. Shengchao Shi
  5. Bin Zheng
  6. Zibin Wang
  7. Xianchi Dong  Is a corresponding author
  8. Peng Zheng  Is a corresponding author
  1. Nanjing University, China
  2. Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, China

Abstract

SARS-CoV-2 is spreading around the world for the past year. Recently, several variants such as B.1.1.7 (Alpha), B.1.351 (Beta), and P.1 (Gamma), sharing a key mutation N501Y on the RBD, appear to be more infectious to humans. To understand the underlying mechanism, we performed cell surface binding assay, kinetics study, single-molecule technique, and computational method to investigate the interaction between these RBD (mutations) and ACE2. Remarkably, RBD with the N501Y mutation exhibited a considerably stronger interaction, with a faster association rate and slower dissociation rate. Consistently, atomic force microscopy-based single-molecule force microscopy quantifies their strength showing a higher binding probability and unbinding force for the mutation. Molecular dynamics simulations of RBD-ACE2 complexes indicated that the N501Y introduced additional π-π and π-cation interaction for the higher force/interaction. Taken together, we suggested that the reinforced interaction from N501Y mutation in RBD should play an essential role in the higher transmission of SARS-CoV-2 variants and future mutations in the RBD of the virus should be under surveillance.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have provided for Figures 1-4.

Article and author information

Author details

  1. Fang Tian

    School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Bei Tong

    Institute of Botany, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, China
    For correspondence
    beitong@cnbg.net
    Competing interests
    The authors declare that no competing interests exist.
  3. Liang Sun

    School of Life Sciences, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Shengchao Shi

    Chemistry and Chemical Engineering, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Bin Zheng

    Chemistry and Chemical Engineering, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Zibin Wang

    School of Life Sciences, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Xianchi Dong

    School of Life Sciences, Nanjing University, Nanjing, China
    For correspondence
    xianchidong@nju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  8. Peng Zheng

    Chemistry and Chemical Engineering, Nanjing University, Nanjing, China
    For correspondence
    pengz@nju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4792-6364

Funding

National Key Research and Development Program of China (2020YFA0509000)

  • Xianchi Dong

Fundamental Research Funds for the Central Universities (14380205)

  • Peng Zheng

Natural Science Foundation of Jiangsu Province (BK20200058)

  • Peng Zheng

Natural Science Foundation of Jiangsu Province (BK20202004)

  • Peng Zheng

Natural Science Foundation of Jiangsu Province (BK20190275)

  • Xianchi Dong

National Natural Science Foundation of China (21771103)

  • Peng Zheng

National Natural Science Foundation of China (21977047)

  • Peng Zheng

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Tian et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Fang Tian
  2. Bei Tong
  3. Liang Sun
  4. Shengchao Shi
  5. Bin Zheng
  6. Zibin Wang
  7. Xianchi Dong
  8. Peng Zheng
(2021)
N501Y mutation of spike protein in SARS-CoV-2 strengthens its binding to receptor ACE2
eLife 10:e69091.
https://doi.org/10.7554/eLife.69091

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https://doi.org/10.7554/eLife.69091