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

被引：11

作者：

Chonira, Vikas ^{[1
]}

Kwon, Young D. ^{[2
]}

Gorman, Jason ^{[2
]}

Case, James Brett ^{[3
]}

Ke, Zhiqiang ^{[4
]}

Simeon, Rudo ^{[1
]}

Cosner, Ryan G. ^{[5
]}

Harris, Darcy R. ^{[2
]}

Olia, Adam S. ^{[2
]}

Stephens, Tyler ^{[6
]}

Shapiro, Lawrence ^{[5
]}

Bender, Michael F. ^{[2
]}

Boyd, Hannah ^{[4
]}

Teng, I-Ting ^{[2
]}

Tsybovsky, Yaroslav ^{[6
]}

Krammer, Florian ^{[7
,8
]}

Zhang, Ningyan ^{[4
]}

Diamond, Michael S. ^{[3
,9
,10
]}

Kwong, Peter D. ^{[2
]}

An, Zhiqiang ^{[4
]}

Chen, Zhilei ^{[1
]}

机构：

[1] Texas A&M Univ, Dept Microbial Pathogenesis & Immunol, Hlth Sci Ctr, Bryan, TX 77807 USA

[2] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[3] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[4] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Texas Therapeut Inst, Houston, TX 77030 USA

[5] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA

[6] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Vaccine Res Ctr, Electron Microscopy Unit,Canc Res Technol Program, Frederick, MD USA

[7] Icahn Sch Med Mt Sinai ISMMS, Dept Microbiol, New York, NY USA

[8] ISMMS, Dept Pathol Mol & Cell Based Med, New York, NY USA

[9] Washington Univ, Sch Med, Dept Pathol & Immunol, Dept Mol Microbiol, St Louis, MO 63110 USA

[10] Washington Univ, Sch Med, Andrew M & Jane M Bursky Ctr Human Immunol & Immu, St Louis, MO 63110 USA

来源：

NATURE CHEMICAL BIOLOGY | 2023年 / 19卷 / 03期

基金：

美国国家卫生研究院;

关键词：

DOMAIN; MODEL; ACE2;

D O I：

10.1038/s41589-022-01193-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 IC(50 )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.

引用

页码：284 / +

页数：15

共 50 条

[21] mRNA vaccines elicit potent neutralization against multiple SARS-CoV-2 omicron subvariants and other variants of concern
Wang, Gang
Shi, Juan
Verma, Abhishek K.
Guan, Xiaoqing
Perlman, Stanley
Du, Lanying
ISCIENCE, 2022, 25 (12)
[22] A potent, broadly protective vaccine against SARS-CoV-2 variants of concern
Wang, Ziyan
An, Jiao
Liu, Kunpeng
Yu, Pin
Fang, Xin
Li, Jiadai
Zhu, Hua
Zhu, Qianjun
Huang, Chuanqi
Zhang, Chao
Zhao, Binbin
Bao, Linlin
Song, Yujiao
Cao, Xiayao
Hu, Dongdong
Jiang, Yuanxiang
Shi, Likang
Zhou, Lingyun
Fan, Jiang
Guan, Wuxiang
Zhou, Chenliang
Hu, Zhongyu
Yuan, Zhiming
Liu, Jiangning
Shan, Chao
Liu, Ge
NPJ VACCINES, 2022, 7 (01)
[23] A highly potent antibody effective against SARS-CoV-2 variants of concern
Fenwick, Craig
Turelli, Priscilla
Perez, Laurent
Pellaton, Celine
Esteves-Leuenberger, Line
Farina, Alex
Campos, Jeremy
Lana, Erica
Fiscalini, Flurin
Raclot, Charlene
Pojer, Florence
Lau, Kelvin
Demurtas, Davide
Descatoire, Marc
Joo, Victor S.
Foglierini, Mathilde
Noto, Alessandra
Abdelnabi, Rana
Foo, Caroline S.
Vangeel, Laura
Neyts, Johan
Du, Wenjuan
Bosch, Berend-Jan
Veldman, Geertruida
Leyssen, Pieter
Thiel, Volker
LeGrand, Roger
Levy, Yves
Trono, Didier
Pantaleo, Giuseppe
CELL REPORTS, 2021, 37 (02):
[24] Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition
Kramer, Kevin J.
Johnson, Nicole, V
Shiakolas, Andrea R.
Suryadevara, Naveenchandra
Periasamy, Sivakumar
Raju, Nagarajan
Williams, Jazmean K.
Wrapp, Daniel
Zost, Seth J.
Walker, Lauren M.
Wall, Steven C.
Holt, Clinton M.
Hsieh, Ching-Lin
Sutton, Rachel E.
Paulo, Ariana
Nargi, Rachel S.
Davidson, Edgar
Doranz, Benjamin J.
Crowe, James E.
Bukreyev, Alexander
Carnahan, Robert H.
McLellan, Jason S.
Georgiev, Ivelin S.
CELL REPORTS, 2021, 37 (01):
[25] Neutralization of SARS-CoV-2 Variants of Concern Harboring Q677H
Zeng, Cong
Evans, John P.
Faraone, Julia N.
Qu, Panke
Zheng, Yi-Min
Saif, Linda
Oltz, Eugene M.
Lozanski, Gerard
Gumina, Richard J.
Liu, Shan-Lu
MBIO, 2021, 12 (05):
[26] A third SARS-CoV-2 spike vaccination improves neutralization of variants-of-concern
Mitch Brinkkemper
Philip J. M. Brouwer
Pauline Maisonnasse
Marloes Grobben
Tom G. Caniels
Meliawati Poniman
Judith A. Burger
Ilja Bontjer
Melissa Oomen
Joey H. Bouhuijs
Cynthia A. van der Linden
Julien Villaudy
Yme U. van der Velden
Kwinten Sliepen
Marit J. van Gils
Roger Le Grand
Rogier W. Sanders
npj Vaccines, 6
[27] The emerging SARS-CoV-2 variants of concern
Sanyaolu, Adekunle
Okorie, Chuku
Marinkovic, Aleksandra
Haider, Nafees
Abbasi, Abu Fahad
Jaferi, Urooj
Prakash, Stephanie
Balendra, Vyshnavy
THERAPEUTIC ADVANCES IN INFECTIOUS DISEASE, 2021, 8
[28] Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera
Vidal, Samuel J.
Collier, Ai-ris Y.
Yu, Jingyou
McMahan, Katherine
Tostanoski, Lisa H.
Ventura, John D.
Aid, Malika
Peter, Lauren
Jacob-Dolan, Catherine
Anioke, Tochi
Chang, Aiquan
Wan, Huahua
Aguayo, Ricardo
Ngo, Debby
Gerszten, Robert E.
Seaman, Michael S.
Barouch, Dan H.
JOURNAL OF VIROLOGY, 2021, 95 (14)
[29] A third SARS-CoV-2 spike vaccination improves neutralization of variants-of-concern
Brinkkemper, Mitch
Brouwer, Philip J. M.
Maisonnasse, Pauline
Grobben, Marloes
Caniels, Tom G.
Poniman, Meliawati
Burger, Judith A.
Bontjer, Ilja
Oomen, Melissa
Bouhuijs, Joey H.
van der Linden, Cynthia A.
Villaudy, Julien
van der Velden, Yme U.
Sliepen, Kwinten
van Gils, Marit J.
Le Grand, Roger
Sanders, Rogier W.
NPJ VACCINES, 2021, 6 (01)
[30] The origin of SARS-CoV-2 variants of concern
Burki, Talha
LANCET INFECTIOUS DISEASES, 2022, 22 (02): : 174 - 175

← 1 2 3 4 5 →