Nature Chemical Biology
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
,
Florian Krammer
7, 8
,
Ningyan Zhang
4
,
Michael S. Diamond
3, 9
,
Peter D. Kwong
2
,
Zhiqiang An
4
,
1
Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, USA
|
4
Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, the University of Texas Health Science Center at Houston, Houston, USA
|
Publication type: Journal Article
Publication date: 2022-11-21
Journal:
Nature Chemical Biology
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 14.8
ISSN: 15524450, 15524469
Molecular Biology
Cell Biology
Abstract
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.
Top-30
Citations by journals
|
1
|
|
|
International Journal of Molecular Sciences
1 publication, 11.11%
|
|
|
Antiviral Research
1 publication, 11.11%
|
|
|
Nature Communications
1 publication, 11.11%
|
|
|
Frontiers in Microbiology
1 publication, 11.11%
|
|
|
Life Science Alliance
1 publication, 11.11%
|
|
|
ACS Pharmacology & Translational Science
1 publication, 11.11%
|
|
|
Annual Review of Chemical and Biomolecular Engineering
1 publication, 11.11%
|
|
|
Russian Chemical Reviews
1 publication, 11.11%
|
|
|
1
|
Citations by publishers
|
1
|
|
|
Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 11.11%
|
|
|
Elsevier
1 publication, 11.11%
|
|
|
Springer Nature
1 publication, 11.11%
|
|
|
Frontiers Media S.A.
1 publication, 11.11%
|
|
|
Cold Spring Harbor Laboratory
1 publication, 11.11%
|
|
|
Rockefeller University Press
1 publication, 11.11%
|
|
|
American Chemical Society (ACS)
1 publication, 11.11%
|
|
|
Annual Reviews
1 publication, 11.11%
|
|
|
Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 11.11%
|
|
|
1
|
- 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.
{"yearsCitations":{"type":"bar","data":{"show":true,"labels":[2023,2024],"ids":[0,0],"codes":[0,0],"imageUrls":["",""],"datasets":[{"label":"Citations number","data":[6,3],"backgroundColor":["#3B82F6","#3B82F6"],"percentage":["66.67","33.33"],"barThickness":null}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":false},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":false}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"journals":{"type":"bar","data":{"show":true,"labels":["International Journal of Molecular Sciences","Antiviral Research","Nature Communications","Frontiers in Microbiology","Life Science Alliance","ACS Pharmacology & Translational Science","Annual Review of Chemical and Biomolecular Engineering","Russian Chemical Reviews"],"ids":[14627,22274,3231,24403,15447,26672,10262,23802],"codes":[0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/lEA1FyUnFAZR1DchuczZi5bjAixG3TNeWVz6oF4R_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/A7oGMwx1m3fFJlKJvQUVra8h0itmEa7JZW0q3Q0b_medium.webp","\/storage\/images\/resized\/9Mus3KG1Tkd7Bwaurt8H3RwWh0CxRlGoO6ng9UK1_medium.webp"],"datasets":[{"label":"","data":[1,1,1,1,1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[11.11,11.11,11.11,11.11,11.11,11.11,11.11,11.11],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":false},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":false}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Journals","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"publishers":{"type":"bar","data":{"show":true,"labels":["Multidisciplinary Digital Publishing Institute (MDPI)","Elsevier","Springer Nature","Frontiers Media S.A.","Cold Spring Harbor Laboratory","Rockefeller University Press","American Chemical Society (ACS)","Annual Reviews","Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii"],"ids":[202,17,8,208,6909,22,40,6941,9422],"codes":[0,0,0,0,0,0,0,0,0],"imageUrls":["\/storage\/images\/resized\/MjH1ITP7lMYGxeqUZfkt2BnVLgjkk413jwBV97XX_medium.webp","\/storage\/images\/resized\/GDnYOu1UpMMfMMRV6Aqle4H0YLLsraeD9IP9qScG_medium.webp","\/storage\/images\/resized\/voXLqlsvTwv5p3iMQ8Dhs95nqB4AXOG7Taj7G4ra_medium.webp","\/storage\/images\/resized\/4QWA67eqfcfyOiA8Wk7YnqroHFqQbTsmDJUYTCTg_medium.webp","\/storage\/images\/resized\/hg4jJjT8wVGtHstBCc0zk465Mg9pLx3G4odCDOqE_medium.webp","\/storage\/images\/resized\/lEA1FyUnFAZR1DchuczZi5bjAixG3TNeWVz6oF4R_medium.webp","\/storage\/images\/resized\/iLiQsFqFaSEx6chlGQ5fbAwF6VYU3WWa08hkss0g_medium.webp","\/storage\/images\/resized\/A7oGMwx1m3fFJlKJvQUVra8h0itmEa7JZW0q3Q0b_medium.webp","\/storage\/images\/resized\/9Mus3KG1Tkd7Bwaurt8H3RwWh0CxRlGoO6ng9UK1_medium.webp"],"datasets":[{"label":"","data":[1,1,1,1,1,1,1,1,1],"backgroundColor":["#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6","#3B82F6"],"percentage":[11.11,11.11,11.11,11.11,11.11,11.11,11.11,11.11,11.11],"barThickness":13}]},"options":{"indexAxis":"y","maintainAspectRatio":false,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":false},"x":{"ticks":{"stepSize":null,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":false}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Publishers","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"yearsCitationsQuartiles":{"type":"bar","data":{"show":true,"labels":[2023,2024],"ids":[],"codes":[],"imageUrls":[],"datasets":[{"label":"Q4","backgroundColor":"rgb(221,90,78)","data":[0,0],"percentage":["0","0"]},{"label":"Q3","backgroundColor":"rgb(251, 163,83)","data":[0,0],"percentage":["0","0"]},{"label":"Q2","backgroundColor":"rgb(232, 213, 89)","data":[0,0],"percentage":["0","0"]},{"label":"Q1","backgroundColor":"rgb(164, 207, 99)","data":[5,3],"percentage":["55.56","33.33"]},{"label":"Quartile not defined","backgroundColor":"#E5E7EB","data":[1,0],"percentage":["11.11","0"]}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":true},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":true}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations quartiles by SCImago per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}},"yearsCitationsQuartilesWs":{"type":"bar","data":{"show":true,"labels":[2023,2024],"ids":[],"codes":[],"imageUrls":[],"datasets":[{"label":"Q4","backgroundColor":"rgb(221,90,78)","data":[0,0],"percentage":["0","0"]},{"label":"Q3","backgroundColor":"rgb(251, 163,83)","data":[0,0],"percentage":["0","0"]},{"label":"Q2","backgroundColor":"rgb(232, 213, 89)","data":[1,0],"percentage":["11.11","0"]},{"label":"Q1","backgroundColor":"rgb(164, 207, 99)","data":[4,2],"percentage":["44.44","22.22"]},{"label":"Quartile not defined","backgroundColor":"#E5E7EB","data":[1,1],"percentage":["11.11","11.11"]}]},"options":{"indexAxis":"x","maintainAspectRatio":true,"scales":{"y":{"ticks":{"precision":0,"autoSkip":false,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":true},"x":{"ticks":{"stepSize":1,"precision":0,"font":{"family":"Montserrat"},"color":"#000000"},"stacked":true}},"plugins":{"legend":{"position":"top","labels":{"font":{"family":"Montserrat"},"color":"#000000"}},"title":{"display":true,"text":"Citations quartiles by WoS per year","font":{"size":24,"family":"Montserrat","weight":600},"color":"#000000"}}}}}
Are you a researcher?
Create a profile to get free access to personal recommendations for colleagues and new articles.
Metrics
Cite this
GOST |
RIS |
BibTex
Cite this
GOST
Copy
Chonira V. et al. A potent and broad neutralization of SARS-CoV-2 variants of concern by DARPins // Nature Chemical Biology. 2022.
GOST all authors (up to 50)
Copy
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.
Cite this
RIS
Copy
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 00:00:00
PB - Springer Nature
SN - 1552-4450
SN - 1552-4469
ER -
Cite this
BibTex
Copy
@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},
publisher = {Springer Nature},
month = {nov},
url = {https://doi.org/10.1038/s41589-022-01193-2},
doi = {10.1038/s41589-022-01193-2}
}
Profiles