Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2021 Jul 27;6(1):284.
doi: 10.1038/s41392-021-00704-2.

N501Y mutation imparts cross-species transmission of SARS-CoV-2 to mice by enhancing receptor binding

Zubiao Niu #  1 , Zhengrong Zhang #  1 , Xiaoyan Gao #  2 , Peng Du #  1 , Jingjing Lu  1 , Bohua Yan  1 , Chenxi Wang  1 , You Zheng  1 , Hongyan Huang  3 , Qiang Sun  4
Affiliations
Comment

N501Y mutation imparts cross-species transmission of SARS-CoV-2 to mice by enhancing receptor binding

Zubiao Niu et al. Signal Transduct Target Ther. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
N501Y S glycoprotein binds to mouse ACE2 to mediate host entry and infection. a Schematic illustration of mutations in the spike protein of three SARS-CoV-2 variants: B.1.1.7, B.1.351 and P.1. Arrow indicates the N501Y mutation that was shared by the three variants in the receptor-binding domain (RBD) of S glycoprotein. b, c Representative images (b) and quantification (c) of syncytia formation upon expression of the indicated S glycoprotein in 293T cells expressing human ACE2 (hACE2) and mouse ACE2 (mACE2), respectively. Scale bars: 200 μm. Data are the mean ± SD of results from 4-5 fields (20x objective lens). ns not significant; ****p < 0.0001. More than three replicates were performed. d Expression of two types of spike proteins in the absence and presence of hACE2 and mACE2 in 293T cells 48 h post transfection by Western blot. FL full length. α-tubulin serves as the loading control. e Expression of the luciferase reporter in 293T-hACE2 and 293T-mACE2 cells upon infection of viruses pseudotyped with N501 or Y501 S glycoproteins as indicated. Data are the mean±SD of triplicate measurements. ns: not significant; ****p < 0.0001. f Three-dimensional structure modeling of the N501 and Y501 S glycoproteins in complexed with hACE2 and mACE2, respectively. The most left image shows the S glycoprotein trimer-ACE2 complex. Zoomed images show the interfaces of different complexes as indicated. The N501, Y501, Y353, and H353 residues are displayed in the style of scaled ball and stick with potential interaction bonds shown in dashed lines. g, h The Fc-tagged N501 (g) and Y501 (h) RBDs of SARS-CoV-2 S glycoprotein bind to His-tagged hACE2 with comparable affinities as determined by the biolayer interferometry analysis. i, j Biolayer interferometry analysis of the binding of His-tagged RBDs to His-tagged mACE2. Though N501 RBD hardly binds to mACE2, the Y501 RBD could effectively bind to mACE2 with a KD of 2.04 × 10−5 M. The resulting data were fit to a 1:1 binding model. Each experiment was repeated independently twice with similar results. Five or six different protein concentrations were used to calculate the KD values. k H&E staining of lung tissue from young (6-weeks old) BALB/c mouse infected with an authentic SARS-CoV-2 virus variant carrying N501Y mutation. Inflammation is evident. Scale bars: 20 and 200 μm, respectively, as indicated. l Immunofluorescent staining of mouse lung tissue infected with an authentic N501Y SARS-CoV-2 variant. Arrows indicate colocalization between ACE2 and S glycoprotein. Scale bars: 100 and 50 μm, respectively, as indicated
See this image and copyright information in PMC

Comment on

  • SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape.
    Li Q, Nie J, Wu J, Zhang L, Ding R, Wang H, Zhang Y, Li T, Liu S, Zhang M, Zhao C, Liu H, Nie L, Qin H, Wang M, Lu Q, Li X, Liu J, Liang H, Shi Y, Shen Y, Xie L, Zhang L, Qu X, Xu W, Huang W, Wang Y. Li Q, et al. Cell. 2021 Apr 29;184(9):2362-2371.e9. doi: 10.1016/j.cell.2021.02.042. Epub 2021 Feb 23. Cell. 2021. PMID: 33735608 Free PMC article.

References

    1. Shi Y, et al. COVID-19 infection: the perspectives on immune responses. Cell Death Differ. 2020;27:1451–1454. doi: 10.1038/s41418-020-0530-3. - DOI - PMC - PubMed
    1. Korber B, et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell. 2020;182:812–827. e19. doi: 10.1016/j.cell.2020.06.043. - DOI - PMC - PubMed
    1. Jiang X, et al. Bimodular effects of D614G mutation on the spike glycoprotein of SARS-CoV-2 enhance protein processing, membrane fusion, and viral infectivity. Signal Transduct. Target Ther. 2020;5:268–271. doi: 10.1038/s41392-020-00392-4. - DOI - PMC - PubMed
    1. Gu H, et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science. 2020;369:1603–1607. doi: 10.1126/science.abc4730. - DOI - PMC - PubMed
    1. Li Q, et al. SARS-CoV-2 501Y.V2 variants lack higher infectivity but do have immune escape. Cell. 2021;184:2362–2371. doi: 10.1016/j.cell.2021.02.042. - DOI - PMC - PubMed

Substances