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
6
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
|
Publication type: Journal Article
Publication date: 2020-10-23
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.
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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)
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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.
Cite this
RIS
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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
SN - 0036-8075
SN - 1095-9203
ER -
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}
}
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.