Nature Chemical Biology

, том 19 , издание 3

A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins

Vikas Chonira ¹

Young Do Kwon ²

Jason Gorman ²

James B. Case ³

Zhiqiang Ku ⁴

Rudo Simeon ¹

Ryan G Casner ⁵

Darcy R. Harris ²

Adam S Olia ²

Tyler Stephens ⁶

Lawrence SHAPIRO ⁵

Michael F Bender ²

Hannah Boyd ⁴

I-Ting Teng ²

Yaroslav Tsybovsky ⁶

Florian Krammer ^{7, 8}

Ningyan Zhang ⁴

Michael S. Diamond ^{3, 9}

Peter D. Kwong ²

Zhiqiang An ⁴

Zhilei Chen ¹

Скрыть аффилиации авторов Показать аффилиации авторов: 9 аффилиаций

Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, USA |

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, USA |

Department of Medicine, Washington University School of Medicine, Saint Louis, USA |

⁴

Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, the University of Texas Health Science Center at Houston, Houston, USA |

⁵

Department of Biochemistry and Molecular Biophysics, Columbia University, New York, USA |

⁶

Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research Inc, Frederick National Laboratory for Cancer Research, Frederick, USA |

⁷

Department of Microbiology, Icahn School of Medicine at Mount Sinai (ISMMS), New York City, USA |

⁸

Department of Pathology, Molecular and Cell based Medicine, ISMMS, New York City, USA |

⁹

Department of Pathology and Immunology, Department of Molecular Microbiology, and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, USA |

Тип публикации: Journal Article

Дата публикации: 2022-11-21

Springer Nature

Nature Chemical Biology

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wos Q1

БС1

SJR: 5.521

CiteScore: 21.5

Impact factor: 13.7

ISSN: 15524450, 15524469

DOI: 10.1038/s41589-022-01193-2

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PubMed ID: 36411391

Molecular Biology

Cell Biology

Краткое описание

We report the engineering and selection of two synthetic proteins—FSR16m and FSR22—for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC50 values of 3.4, 2.2 and 7.4 ng ml−1 for FSR16m. Cryo-EM structures revealed that these DARPins recognize a region of the receptor-binding domain (residues 456, 475, 486, 487 and 489) overlapping a critical portion of the angiotensin-converting enzyme 2 (ACE2)-binding surface. K18-hACE2 transgenic mice inoculated with B.1.617.2 and receiving intranasally administered FSR16m showed less weight loss and 10–100-fold lower viral burden in upper and lower respiratory tracts. The strong and broad neutralization potency makes FSR16m and FSR22 promising candidates for the prevention and treatment of infection by SARS-CoV-2. Homotrimeric DARPin molecules neutralize SARS-CoV-2 variants of concern by targeting a critical ACE2-binding interface.

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Chonira V. et al. A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins // Nature Chemical Biology. 2022. Vol. 19. No. 3.

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Chonira V., Kwon Y. D., Gorman J., Case J. B., Ku Z., Simeon R., Casner R. G., Harris D. R., Olia A. S., Stephens T., SHAPIRO L., Bender M. F., Boyd H., Teng I., Tsybovsky Y., Krammer F., Zhang N., Diamond M. S., Kwong P. D., An Z., Chen Z. A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins // Nature Chemical Biology. 2022. Vol. 19. No. 3.

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TY - JOUR

DO - 10.1038/s41589-022-01193-2

UR - https://doi.org/10.1038/s41589-022-01193-2

TI - A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins

T2 - Nature Chemical Biology

AU - Chonira, Vikas

AU - Kwon, Young Do

AU - Gorman, Jason

AU - Case, James B.

AU - Ku, Zhiqiang

AU - Simeon, Rudo

AU - Casner, Ryan G

AU - Harris, Darcy R.

AU - Olia, Adam S

AU - Stephens, Tyler

AU - SHAPIRO, Lawrence

AU - Bender, Michael F

AU - Boyd, Hannah

AU - Teng, I-Ting

AU - Tsybovsky, Yaroslav

AU - Krammer, Florian

AU - Zhang, Ningyan

AU - Diamond, Michael S.

AU - Kwong, Peter D.

AU - An, Zhiqiang

AU - Chen, Zhilei

PY - 2022

DA - 2022/11/21

PB - Springer Nature

IS - 3

VL - 19

PMID - 36411391

SN - 1552-4450

SN - 1552-4469

ER -

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@article{2022_Chonira,

author = {Vikas Chonira and Young Do Kwon and Jason Gorman and James B. Case and Zhiqiang Ku and Rudo Simeon and Ryan G Casner and Darcy R. Harris and Adam S Olia and Tyler Stephens and Lawrence SHAPIRO and Michael F Bender and Hannah Boyd and I-Ting Teng and Yaroslav Tsybovsky and Florian Krammer and Ningyan Zhang and Michael S. Diamond and Peter D. Kwong and Zhiqiang An and Zhilei Chen},

title = {A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins},

journal = {Nature Chemical Biology},

year = {2022},

volume = {19},

publisher = {Springer Nature},

month = {nov},

url = {https://doi.org/10.1038/s41589-022-01193-2},

number = {3},

doi = {10.1038/s41589-022-01193-2}

}

Издатель

Springer Nature

Журнал

Nature Chemical Biology

scimago Q1

wos Q1

БС1

SJR

5.521

CiteScore

21.5

Impact factor

13.7

ISSN

15524450 (Print)

15524469 (Electronic)

Профили

Квонг Петер