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 ¹

Young-Jun Park ¹

Eva M. Strauch ⁶

Lance L. Stewart ^{1, 2}

Michael S. Diamond ^{4, 7}

David Veesler ¹

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

Hide authors affiliations Show authors affiliations: 8 affiliations

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

Institute for Protein Design, 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)

Science

scimago Q1

wos Q1

SJR: 10.416

CiteScore: 48.4

Impact factor: 45.8

ISSN: 00368075, 10959203

DOI: 10.1126/science.abd9909

Copy DOI

PubMed ID: 32907861

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

Found

1 citation

Osolodkin Dmitry

🥼 🤝

PhD in Chemistry

80 publications, 1 707 citations

h-index: 22

Sechenov First Moscow State Medical University

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences

1 citation

Kar Abhisek

6 publications, 54 citations

h-index: 3

Tata Institute of Fundamental Research

Research interests

Chemical biology

Synthetic Chemistry

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GOST Copy

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

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

SP - 426-431

IS - 6515

VL - 370

PMID - 32907861

SN - 0036-8075

SN - 1095-9203

ER -

BibTex |

Cite this

BibTex (up to 50 authors) 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

Cite this

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.

Publisher

American Association for the Advancement of Science (AAAS)

Journal

Science

scimago Q1

wos Q1

SJR

10.416

CiteScore

48.4

Impact factor

45.8

ISSN

00368075 (Print)

10959203 (Electronic)