Nature Chemical Biology, volume 18, issue 10, pages 1046-1055
A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein
Bhavesh Khatri
1
,
Ishika Pramanick
1
,
Sameer Kumar Malladi
1
,
Raju S Rajmani
1
,
Sahil Kumar
2
,
Pritha Ghosh
1
,
Nayanika Sengupta
1
,
R Rahisuddin
3
,
Narender Kumar
3
,
Kumaran Sinnaeruvadi
3
,
Rajesh P Ringe
2
,
Raghavan VARADARAJAN
1
,
Somnath Dutta
1
,
Jayanta Chatterjee
1
Publication type: Journal Article
Publication date: 2022-06-02
Journal:
Nature Chemical Biology
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 14.8
ISSN: 15524450, 15524469
Molecular Biology
Cell Biology
Abstract
Protein tertiary structure mimetics are valuable tools to target large protein–protein interaction interfaces. Here, we demonstrate a strategy for designing dimeric helix-hairpin motifs from a previously reported three-helix-bundle miniprotein that targets the receptor-binding domain (RBD) of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Through truncation of the third helix and optimization of the interhelical loop residues of the miniprotein, we developed a thermostable dimeric helix-hairpin. The dimeric four-helix bundle competes with the human angiotensin-converting enzyme 2 (ACE2) in binding to RBD with 2:2 stoichiometry. Cryogenic-electron microscopy revealed the formation of dimeric spike ectodomain trimer by the four-helix bundle, where all the three RBDs from either spike protein are attached head-to-head in an open conformation, revealing a novel mechanism for virus neutralization. The proteomimetic protects hamsters from high dose viral challenge with replicative SARS-CoV-2 viruses, demonstrating the promise of this class of peptides that inhibit protein–protein interaction through target dimerization. A redesigned antiviral miniprotein based on a dimeric helix-hairpin motif binds and dimerizes the RBD of the SARS-CoV-2 spike protein and inhibits viral infection by inhibiting spike interaction with ACE2.
Top-30
Citations by journals
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The Lancet Microbe
1 publication, 10%
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Doklady Biochemistry and Biophysics
1 publication, 10%
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Journal of Virology
1 publication, 10%
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ChemBioChem
1 publication, 10%
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Frontiers in Molecular Biosciences
1 publication, 10%
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ACS Chemical Biology
1 publication, 10%
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Russian Chemical Reviews
1 publication, 10%
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Citations by publishers
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1
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Elsevier
1 publication, 10%
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Pleiades Publishing
1 publication, 10%
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American Society for Microbiology
1 publication, 10%
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Wiley
1 publication, 10%
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Frontiers Media S.A.
1 publication, 10%
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American Chemical Society (ACS)
1 publication, 10%
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Cold Spring Harbor Laboratory
1 publication, 10%
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Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 10%
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- We do not take into account publications without a DOI.
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- Statistics recalculated weekly.
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Khatri B. et al. A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein // Nature Chemical Biology. 2022. Vol. 18. No. 10. pp. 1046-1055.
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Khatri B., Pramanick I., Malladi S. K., Rajmani R. S., Kumar S., Ghosh P., Sengupta N., Rahisuddin R., Kumar N., Sinnaeruvadi K., Ringe R. P., VARADARAJAN R., Dutta S., Chatterjee J. A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein // Nature Chemical Biology. 2022. Vol. 18. No. 10. pp. 1046-1055.
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TY - JOUR
DO - 10.1038/s41589-022-01060-0
UR - https://doi.org/10.1038/s41589-022-01060-0
TI - A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein
T2 - Nature Chemical Biology
AU - Khatri, Bhavesh
AU - Pramanick, Ishika
AU - Malladi, Sameer Kumar
AU - Rajmani, Raju S
AU - Kumar, Sahil
AU - Ghosh, Pritha
AU - Sengupta, Nayanika
AU - Rahisuddin, R
AU - Kumar, Narender
AU - Sinnaeruvadi, Kumaran
AU - Ringe, Rajesh P
AU - VARADARAJAN, Raghavan
AU - Dutta, Somnath
AU - Chatterjee, Jayanta
PY - 2022
DA - 2022/06/02 00:00:00
PB - Springer Nature
SP - 1046-1055
IS - 10
VL - 18
SN - 1552-4450
SN - 1552-4469
ER -
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@article{2022_Khatri,
author = {Bhavesh Khatri and Ishika Pramanick and Sameer Kumar Malladi and Raju S Rajmani and Sahil Kumar and Pritha Ghosh and Nayanika Sengupta and R Rahisuddin and Narender Kumar and Kumaran Sinnaeruvadi and Rajesh P Ringe and Raghavan VARADARAJAN and Somnath Dutta and Jayanta Chatterjee},
title = {A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein},
journal = {Nature Chemical Biology},
year = {2022},
volume = {18},
publisher = {Springer Nature},
month = {jun},
url = {https://doi.org/10.1038/s41589-022-01060-0},
number = {10},
pages = {1046--1055},
doi = {10.1038/s41589-022-01060-0}
}
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Khatri, Bhavesh, et al. “A dimeric proteomimetic prevents SARS-CoV-2 infection by dimerizing the spike protein.” Nature Chemical Biology, vol. 18, no. 10, Jun. 2022, pp. 1046-1055. https://doi.org/10.1038/s41589-022-01060-0.