Nature Reviews Molecular Cell Biology, volume 23, issue 1, pages 3-20

Mechanisms of SARS-CoV-2 entry into cells

Cody B Jackson ^{1, 2}

Michael Farzan ¹

Bing Chen ^{3, 4}

Hyeryun Choe ¹

Hide authors affiliations Show authors affiliations: 4 affiliations

Department of Immunology and Microbiology, Scripps Research, Jupiter, USA |

Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, USA |

Division of Molecular Medicine, Boston Children’s Hospital, Boston, USA |

⁴

Department of Pediatrics, Harvard Medical School, Boston, USA |

Publication type: Journal Article

Publication date: 2021-10-05

Springer Nature

Journal: Nature Reviews Molecular Cell Biology

Quartile SCImago

Quartile WOS

Impact factor: 112.7

ISSN: 14710072, 14710080

DOI: 10.1038/s41580-021-00418-x

Copy DOI

PubMed ID: 34611326

Molecular Biology

Cell Biology

Abstract

The unprecedented public health and economic impact of the COVID-19 pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been met with an equally unprecedented scientific response. Much of this response has focused, appropriately, on the mechanisms of SARS-CoV-2 entry into host cells, and in particular the binding of the spike (S) protein to its receptor, angiotensin-converting enzyme 2 (ACE2), and subsequent membrane fusion. This Review provides the structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the S protein with ACE2, engagement of the receptor-binding domain of the S protein with ACE2, proteolytic activation of the S protein, endocytosis and membrane fusion. We define the roles of furin-like proteases, transmembrane protease, serine 2 (TMPRSS2) and cathepsin L in these processes, and delineate the features of ACE2 orthologues in reservoir animal species and S protein adaptations that facilitate efficient human transmission. We also examine the utility of vaccines, antibodies and other potential therapeutics targeting SARS-CoV-2 entry mechanisms. Finally, we present key outstanding questions associated with this critical process. Entry of SARS-CoV-2 into host cells is mediated by the interaction between the viral spike protein and its receptor angiotensin-converting enzyme 2, followed by virus–cell membrane fusion. Worldwide research efforts have provided a detailed understanding of this process at the structural and cellular levels, enabling successful vaccine development for a rapid response to the COVID-19 pandemic.

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Citations by journals

	10 20 30 40 50 60 70 80 90
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 84, 4.88% International Journal of Molecular Sciences 84 publications, 4.88%
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Frontiers in Immunology	Frontiers in Immunology, 48, 2.79% Frontiers in Immunology 48 publications, 2.79%
Vaccines	Vaccines, 23, 1.33% Vaccines 23 publications, 1.33%
Scientific Reports	Scientific Reports, 22, 1.28% Scientific Reports 22 publications, 1.28%
Nature Communications	Nature Communications, 21, 1.22% Nature Communications 21 publications, 1.22%
Journal of Virology	Journal of Virology, 19, 1.1% Journal of Virology 19 publications, 1.1%
Cells	Cells, 18, 1.04% Cells 18 publications, 1.04%
Journal of Medical Virology	Journal of Medical Virology, 18, 1.04% Journal of Medical Virology 18 publications, 1.04%
Biomedicines	Biomedicines, 14, 0.81% Biomedicines 14 publications, 0.81%
Frontiers in Cellular and Infection Microbiology	Frontiers in Cellular and Infection Microbiology, 14, 0.81% Frontiers in Cellular and Infection Microbiology 14 publications, 0.81%
Frontiers in Microbiology	Frontiers in Microbiology, 14, 0.81% Frontiers in Microbiology 14 publications, 0.81%
Antiviral Research	Antiviral Research, 13, 0.75% Antiviral Research 13 publications, 0.75%
Heliyon	Heliyon, 13, 0.75% Heliyon 13 publications, 0.75%
mBio	mBio, 12, 0.7% mBio 12 publications, 0.7%
Proceedings of the National Academy of Sciences of the United States of America	Proceedings of the National Academy of Sciences of the United States of America, 12, 0.7% Proceedings of the National Academy of Sciences of the United States of America 12 publications, 0.7%
Microorganisms	Microorganisms, 11, 0.64% Microorganisms 11 publications, 0.64%
iScience	iScience, 11, 0.64% iScience 11 publications, 0.64%
Microbiology spectrum	Microbiology spectrum, 11, 0.64% Microbiology spectrum 11 publications, 0.64%
PLoS Pathogens	PLoS Pathogens, 10, 0.58% PLoS Pathogens 10 publications, 0.58%
Journal of Biomolecular Structure and Dynamics	Journal of Biomolecular Structure and Dynamics, 10, 0.58% Journal of Biomolecular Structure and Dynamics 10 publications, 0.58%
Frontiers in Pharmacology	Frontiers in Pharmacology, 10, 0.58% Frontiers in Pharmacology 10 publications, 0.58%
Signal Transduction and Targeted Therapy	Signal Transduction and Targeted Therapy, 10, 0.58% Signal Transduction and Targeted Therapy 10 publications, 0.58%
Life	Life, 9, 0.52% Life 9 publications, 0.52%
Journal of Clinical Medicine	Journal of Clinical Medicine, 9, 0.52% Journal of Clinical Medicine 9 publications, 0.52%
Frontiers in Molecular Biosciences	Frontiers in Molecular Biosciences, 9, 0.52% Frontiers in Molecular Biosciences 9 publications, 0.52%
Molecules	Molecules, 9, 0.52% Molecules 9 publications, 0.52%
ACS Omega	ACS Omega, 9, 0.52% ACS Omega 9 publications, 0.52%
Pathogens	Pathogens, 8, 0.46% Pathogens 8 publications, 0.46%
	10 20 30 40 50 60 70 80 90

Citations by publishers

	50 100 150 200 250 300 350
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 339, 19.67% Multidisciplinary Digital Publishing Institute (MDPI) 339 publications, 19.67%
Elsevier	Elsevier, 299, 17.35% Elsevier 299 publications, 17.35%
Springer Nature	Springer Nature, 237, 13.76% Springer Nature 237 publications, 13.76%
Frontiers Media S.A.	Frontiers Media S.A., 133, 7.72% Frontiers Media S.A. 133 publications, 7.72%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 128, 7.43% Cold Spring Harbor Laboratory 128 publications, 7.43%
Wiley	Wiley, 92, 5.34% Wiley 92 publications, 5.34%
American Chemical Society (ACS)	American Chemical Society (ACS), 69, 4% American Chemical Society (ACS) 69 publications, 4%
American Society for Microbiology	American Society for Microbiology, 47, 2.73% American Society for Microbiology 47 publications, 2.73%
Taylor & Francis	Taylor & Francis, 34, 1.97% Taylor & Francis 34 publications, 1.97%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 21, 1.22% Public Library of Science (PLoS) 21 publications, 1.22%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 19, 1.1% Royal Society of Chemistry (RSC) 19 publications, 1.1%
Oxford University Press	Oxford University Press, 19, 1.1% Oxford University Press 19 publications, 1.1%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 13, 0.75% American Association for the Advancement of Science (AAAS) 13 publications, 0.75%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 12, 0.7% Proceedings of the National Academy of Sciences (PNAS) 12 publications, 0.7%
Bentham Science	Bentham Science, 11, 0.64% Bentham Science 11 publications, 0.64%
Wolters Kluwer Health	Wolters Kluwer Health, 10, 0.58% Wolters Kluwer Health 10 publications, 0.58%
Baishideng Publishing Group	Baishideng Publishing Group, 9, 0.52% Baishideng Publishing Group 9 publications, 0.52%
Mary Ann Liebert	Mary Ann Liebert, 8, 0.46% Mary Ann Liebert 8 publications, 0.46%
SAGE	SAGE, 8, 0.46% SAGE 8 publications, 0.46%
Pleiades Publishing	Pleiades Publishing, 8, 0.46% Pleiades Publishing 8 publications, 0.46%
Research Square Platform LLC	Research Square Platform LLC, 8, 0.46% Research Square Platform LLC 8 publications, 0.46%
eLife Sciences Publications	eLife Sciences Publications, 8, 0.46% eLife Sciences Publications 8 publications, 0.46%
S. Karger AG	S. Karger AG, 6, 0.35% S. Karger AG 6 publications, 0.35%
Dove Medical Press	Dove Medical Press, 5, 0.29% Dove Medical Press 5 publications, 0.29%
The Endocrine Society	The Endocrine Society, 4, 0.23% The Endocrine Society 4 publications, 0.23%
F1000 Research	F1000 Research, 4, 0.23% F1000 Research 4 publications, 0.23%
Thieme	Thieme, 4, 0.23% Thieme 4 publications, 0.23%
American Physiological Society	American Physiological Society, 4, 0.23% American Physiological Society 4 publications, 0.23%
Annual Reviews	Annual Reviews, 4, 0.23% Annual Reviews 4 publications, 0.23%
	50 100 150 200 250 300 350

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Jackson C. B. et al. Mechanisms of SARS-CoV-2 entry into cells // Nature Reviews Molecular Cell Biology. 2021. Vol. 23. No. 1. pp. 3-20.

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Jackson C. B., Farzan M., Chen B., Choe H. Mechanisms of SARS-CoV-2 entry into cells // Nature Reviews Molecular Cell Biology. 2021. Vol. 23. No. 1. pp. 3-20.

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TY - JOUR

DO - 10.1038/s41580-021-00418-x

UR - https://doi.org/10.1038/s41580-021-00418-x

TI - Mechanisms of SARS-CoV-2 entry into cells

T2 - Nature Reviews Molecular Cell Biology

AU - Jackson, Cody B

AU - Farzan, Michael

AU - Chen, Bing

AU - Choe, Hyeryun

PY - 2021

DA - 2021/10/05 00:00:00

PB - Springer Nature

SP - 3-20

IS - 1

VL - 23

PMID - 34611326

SN - 1471-0072

SN - 1471-0080

ER -

BibTex |

Cite this

BibTex Copy

@article{2021_Jackson,

author = {Cody B Jackson and Michael Farzan and Bing Chen and Hyeryun Choe},

title = {Mechanisms of SARS-CoV-2 entry into cells},

journal = {Nature Reviews Molecular Cell Biology},

year = {2021},

volume = {23},

publisher = {Springer Nature},

month = {oct},

url = {https://doi.org/10.1038/s41580-021-00418-x},

number = {1},

pages = {3--20},

doi = {10.1038/s41580-021-00418-x}

}

MLA

Cite this

MLA Copy

Jackson, Cody B., et al. “Mechanisms of SARS-CoV-2 entry into cells.” Nature Reviews Molecular Cell Biology, vol. 23, no. 1, Oct. 2021, pp. 3-20. https://doi.org/10.1038/s41580-021-00418-x.

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Publisher

Springer Nature

Journal

Nature Reviews Molecular Cell Biology

Quartile SCImago

Quartile WOS

Impact factor

112.7

ISSN

14710072 (Print)
14710080 (Electronic)