Open Access

Science, volume 370, issue 6515, pages 426-431

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors

Longxing Cao ^{1, 2}

Inna Goreshnik ^{1, 2}

Brian Coventry ^{1, 2, 3}

James B. Case ⁴

Lauren Miller ^{1, 2}

Lisa Kozodoy ^{1, 2}

Rita E. Chen ^{4, 5}

Lauren Carter ^{1, 2}

Alexandra C Walls ²

Young-Jun Park ²

Eva M. Strauch ⁶

Lance L. Stewart ^{1, 2}

Michael S. Diamond ^{4, 7}

David Veesler ²

David G. Baker ^{1, 2, 8}

Hide authors affiliations Show authors affiliations: 8 affiliations

Institute for Protein Design, University of Washington, Seattle, WA 98195, USA. |

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. |

Molecular Engineering Graduate Program, University of Washington, Seattle, WA 98195, USA. |

⁴

Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. |

⁵

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. |

⁶

Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA. |

⁷

The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. |

⁸

Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

University of Washington

Howard Hughes Medical Institute

Publication type: Journal Article

Publication date: 2020-10-23

American Association for the Advancement of Science (AAAS)

Journal: Science

Quartile SCImago

Quartile WOS

Impact factor: 56.9

ISSN: 00368075, 10959203

DOI: 10.1126/science.abd9909

Copy DOI

Multidisciplinary

Abstract

Miniproteins against SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is decorated with spikes, and viral entry into cells is initiated when these spikes bind to the host angiotensin-converting enzyme 2 (ACE2) receptor. Many monoclonal antibody therapies in development target the spike proteins. Cao et al. designed small, stable proteins that bind tightly to the spike and block it from binding to ACE2. The best designs bind with very high affinity and prevent SARS-CoV-2 infection of mammalian Vero E6 cells. Cryo–electron microscopy shows that the structures of the two most potent inhibitors are nearly identical to the computational models. Unlike antibodies, the miniproteins do not require expression in mammalian cells, and their small size and high stability may allow formulation for direct delivery to the nasal or respiratory system.

Science , this issue p. 426

By date By citations

Top-30

Citations by journals

	2 4 6 8 10 12 14 16
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 16, 3.21% International Journal of Molecular Sciences 16 publications, 3.21%
Viruses	Viruses, 12, 2.41% Viruses 12 publications, 2.41%
Nature Communications	Nature Communications, 9, 1.81% Nature Communications 9 publications, 1.81%
Proteins: Structure, Function and Genetics	Proteins: Structure, Function and Genetics, 9, 1.81% Proteins: Structure, Function and Genetics 9 publications, 1.81%
Journal of Physical Chemistry B	Journal of Physical Chemistry B, 8, 1.61% Journal of Physical Chemistry B 8 publications, 1.61%
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, 8, 1.61% Proceedings of the National Academy of Sciences of the United States of America 8 publications, 1.61%
Scientific Reports	Scientific Reports, 7, 1.41% Scientific Reports 7 publications, 1.41%
Computational and Structural Biotechnology Journal	Computational and Structural Biotechnology Journal, 7, 1.41% Computational and Structural Biotechnology Journal 7 publications, 1.41%
Protein Science	Protein Science, 7, 1.41% Protein Science 7 publications, 1.41%
Journal of Biomolecular Structure and Dynamics	Journal of Biomolecular Structure and Dynamics, 7, 1.41% Journal of Biomolecular Structure and Dynamics 7 publications, 1.41%
Current Opinion in Structural Biology	Current Opinion in Structural Biology, 6, 1.2% Current Opinion in Structural Biology 6 publications, 1.2%
Frontiers in Molecular Biosciences	Frontiers in Molecular Biosciences, 5, 1% Frontiers in Molecular Biosciences 5 publications, 1%
Frontiers in Immunology	Frontiers in Immunology, 5, 1% Frontiers in Immunology 5 publications, 1%
Briefings in Bioinformatics	Briefings in Bioinformatics, 5, 1% Briefings in Bioinformatics 5 publications, 1%
Journal of Chemical Information and Modeling	Journal of Chemical Information and Modeling, 5, 1% Journal of Chemical Information and Modeling 5 publications, 1%
Frontiers in Microbiology	Frontiers in Microbiology, 4, 0.8% Frontiers in Microbiology 4 publications, 0.8%
Nature Structural and Molecular Biology	Nature Structural and Molecular Biology, 4, 0.8% Nature Structural and Molecular Biology 4 publications, 0.8%
Nature	Nature, 4, 0.8% Nature 4 publications, 0.8%
Nature Chemical Biology	Nature Chemical Biology, 4, 0.8% Nature Chemical Biology 4 publications, 0.8%
Cell Reports	Cell Reports, 4, 0.8% Cell Reports 4 publications, 0.8%
PLoS ONE	PLoS ONE, 4, 0.8% PLoS ONE 4 publications, 0.8%
Biophysical Journal	Biophysical Journal, 4, 0.8% Biophysical Journal 4 publications, 0.8%
Protein Engineering, Design and Selection	Protein Engineering, Design and Selection, 4, 0.8% Protein Engineering, Design and Selection 4 publications, 0.8%
Frontiers in Drug Discovery	Frontiers in Drug Discovery, 3, 0.6% Frontiers in Drug Discovery 3 publications, 0.6%
Communications Biology	Communications Biology, 3, 0.6% Communications Biology 3 publications, 0.6%
Journal of Molecular Modeling	Journal of Molecular Modeling, 3, 0.6% Journal of Molecular Modeling 3 publications, 0.6%
ACS Central Science	ACS Central Science, 3, 0.6% ACS Central Science 3 publications, 0.6%
Structure	Structure, 3, 0.6% Structure 3 publications, 0.6%
Chemical Engineering Journal	Chemical Engineering Journal, 3, 0.6% Chemical Engineering Journal 3 publications, 0.6%
	2 4 6 8 10 12 14 16

Citations by publishers

	10 20 30 40 50 60 70 80 90 100
Elsevier	Elsevier, 97, 19.48% Elsevier 97 publications, 19.48%
Springer Nature	Springer Nature, 70, 14.06% Springer Nature 70 publications, 14.06%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 69, 13.86% Cold Spring Harbor Laboratory 69 publications, 13.86%
American Chemical Society (ACS)	American Chemical Society (ACS), 57, 11.45% American Chemical Society (ACS) 57 publications, 11.45%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 43, 8.63% Multidisciplinary Digital Publishing Institute (MDPI) 43 publications, 8.63%
Wiley	Wiley, 35, 7.03% Wiley 35 publications, 7.03%
Frontiers Media S.A.	Frontiers Media S.A., 25, 5.02% Frontiers Media S.A. 25 publications, 5.02%
Oxford University Press	Oxford University Press, 16, 3.21% Oxford University Press 16 publications, 3.21%
Taylor & Francis	Taylor & Francis, 14, 2.81% Taylor & Francis 14 publications, 2.81%
Royal Society of Chemistry (RSC)	Royal Society of Chemistry (RSC), 13, 2.61% Royal Society of Chemistry (RSC) 13 publications, 2.61%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 8, 1.61% American Association for the Advancement of Science (AAAS) 8 publications, 1.61%
Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 8, 1.61% Proceedings of the National Academy of Sciences (PNAS) 8 publications, 1.61%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 5, 1% Public Library of Science (PLoS) 5 publications, 1%
American Society for Microbiology	American Society for Microbiology, 5, 1% American Society for Microbiology 5 publications, 1%
Biophysical Society	Biophysical Society, 3, 0.6% Biophysical Society 3 publications, 0.6%
American Institute of Physics (AIP)	American Institute of Physics (AIP), 2, 0.4% American Institute of Physics (AIP) 2 publications, 0.4%
Mary Ann Liebert	Mary Ann Liebert, 2, 0.4% Mary Ann Liebert 2 publications, 0.4%
American Society for Clinical Investigation	American Society for Clinical Investigation, 1, 0.2% American Society for Clinical Investigation 1 publication, 0.2%
American Society for Pharmacology and Experimental Therapeutics	American Society for Pharmacology and Experimental Therapeutics, 1, 0.2% American Society for Pharmacology and Experimental Therapeutics 1 publication, 0.2%
The Chemical Society of Japan	The Chemical Society of Japan, 1, 0.2% The Chemical Society of Japan 1 publication, 0.2%
Portland Press	Portland Press, 1, 0.2% Portland Press 1 publication, 0.2%
Spandidos Publications	Spandidos Publications, 1, 0.2% Spandidos Publications 1 publication, 0.2%
American Society for Biochemistry and Molecular Biology	American Society for Biochemistry and Molecular Biology, 1, 0.2% American Society for Biochemistry and Molecular Biology 1 publication, 0.2%
Wolters Kluwer Health	Wolters Kluwer Health, 1, 0.2% Wolters Kluwer Health 1 publication, 0.2%
Rockefeller University Press	Rockefeller University Press, 1, 0.2% Rockefeller University Press 1 publication, 0.2%
Chinese Center for Disease Control and Prevention	Chinese Center for Disease Control and Prevention, 1, 0.2% Chinese Center for Disease Control and Prevention 1 publication, 0.2%
Pleiades Publishing	Pleiades Publishing, 1, 0.2% Pleiades Publishing 1 publication, 0.2%
Impact Journals	Impact Journals, 1, 0.2% Impact Journals 1 publication, 0.2%
Association for Computing Machinery (ACM)	Association for Computing Machinery (ACM), 1, 0.2% Association for Computing Machinery (ACM) 1 publication, 0.2%
	10 20 30 40 50 60 70 80 90 100

We do not take into account publications without a DOI.
Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
Statistics recalculated weekly.

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Cao L. et al. De novo design of picomolar SARS-CoV-2 miniprotein inhibitors // Science. 2020. Vol. 370. No. 6515. pp. 426-431.

GOST all authors (up to 50) Copy

Cao L., Goreshnik I., Coventry B., Case J. B., Miller L., Kozodoy L., Chen R. E., Carter L., Walls A. C., Park Y., Strauch E. M., Stewart L. L., Diamond M. S., Veesler D., Baker D. G. De novo design of picomolar SARS-CoV-2 miniprotein inhibitors // Science. 2020. Vol. 370. No. 6515. pp. 426-431.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1126/science.abd9909

UR - https://doi.org/10.1126/science.abd9909

TI - De novo design of picomolar SARS-CoV-2 miniprotein inhibitors

T2 - Science

AU - Cao, Longxing

AU - Goreshnik, Inna

AU - Coventry, Brian

AU - Case, James B.

AU - Miller, Lauren

AU - Kozodoy, Lisa

AU - Chen, Rita E.

AU - Carter, Lauren

AU - Walls, Alexandra C

AU - Park, Young-Jun

AU - Strauch, Eva M.

AU - Stewart, Lance L.

AU - Diamond, Michael S.

AU - Veesler, David

AU - Baker, David G.

PY - 2020

DA - 2020/10/23 00:00:00

PB - American Association for the Advancement of Science (AAAS)

SP - 426-431

IS - 6515

VL - 370

SN - 0036-8075

SN - 1095-9203

ER -

BibTex |

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BibTex Copy

@article{2020_Cao,

author = {Longxing Cao and Inna Goreshnik and Brian Coventry and James B. Case and Lauren Miller and Lisa Kozodoy and Rita E. Chen and Lauren Carter and Alexandra C Walls and Young-Jun Park and Eva M. Strauch and Lance L. Stewart and Michael S. Diamond and David Veesler and David G. Baker},

title = {De novo design of picomolar SARS-CoV-2 miniprotein inhibitors},

journal = {Science},

year = {2020},

volume = {370},

publisher = {American Association for the Advancement of Science (AAAS)},

month = {oct},

url = {https://doi.org/10.1126/science.abd9909},

number = {6515},

pages = {426--431},

doi = {10.1126/science.abd9909}

}

MLA

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MLA Copy

Cao, Longxing, et al. “De novo design of picomolar SARS-CoV-2 miniprotein inhibitors.” Science, vol. 370, no. 6515, Oct. 2020, pp. 426-431. https://doi.org/10.1126/science.abd9909.

Found error?

Publisher

American Association for the Advancement of Science (AAAS)

Journal

Science

Quartile SCImago

Quartile WOS

Impact factor

56.9

ISSN

00368075 (Print)
10959203 (Electronic)