A bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants

被引：0

作者：

Kim, Dong-Gun ^{[1
,9
]}

Kim, Uijin ^{[2
]}

Park, In Ho ^{[4
,5
]}

Ryu, Bumhan ^{[7
]}

Yoo, Youngki ^{[2
]}

Cha, Jeong Seok ^{[2
,10
]}

Yoon, Ga-Yeon ^{[2
]}

Kim, Sung-Hee ^{[5
,6
]}

Oh, Heeju ^{[5
,6
]}

Seo, Jun-Young ^{[5
,6
]}

Nam, Ki Taek ^{[5
,6
]}

Seong, Je Kyung ^{[8
]}

Shin, Jeon-Soo ^{[3
,4
,5
,6
]}

Cho, Hyun-Soo ^{[2
]}

Kim, Hak-Sung ^{[1
]}

机构：

[1] Korea Adv Inst Sci & Technol KAIST, Dept Biol Sci, Daejeon 34141, South Korea

[2] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Syst Biol, Seoul 03722, South Korea

[3] Yonsei Univ, Coll Med, Dept Microbiol, Seoul 03722, South Korea

[4] Yonsei Univ, Coll Med, Inst Immunol & Immunol Dis, Seoul 03722, South Korea

[5] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 03722, South Korea

[6] Yonsei Univ, Coll Med, Brain Korea 21 Project Med Sci, Seoul 03722, South Korea

[7] Inst Basic Sci IBS, Daejeon 34126, South Korea

[8] Seoul Natl Univ, Korea Mouse Phenotyping Ctr, Seoul 08826, South Korea

[9] Samsung Bioepis, Cell line Dev Team, Incheon 21987, South Korea

[10] Chung Ang Univ, Res Inst Pharm, Seoul 06974, South Korea

来源：

ANTIVIRAL RESEARCH | 2023年 / 220卷

基金：

新加坡国家研究基金会;

关键词：

Severe acute respiratory syndrome coronavirus; 2 (SARS-CoV-2); Repebody; Synthetic antibody; Receptor binding domain (RBD) variant; Cryo-EM; RECEPTOR-BINDING DOMAIN; PROTEIN BINDER; MUTATIONS; AFFINITY; ACE2;

D O I：

10.1016/j.antiviral.2023.105738

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Coronavirus Disease 2019 (COVID-19) pandemic is severely impacting the world, and tremendous efforts have been made to deal with it. Despite many advances in vaccines and therapeutics, severe acute respiratory syn-drome coronavirus 2 (SARS-CoV-2) variants remains an intractable challenge. We present a bivalent Receptor Binding Domain (RBD)-specific synthetic antibody, specific for the RBD of wild-type (lineage A), developed from a non-antibody protein scaffold composed of LRR (Leucine-rich repeat) modules through phage display. We further reinforced the unique feature of the synthetic antibody by constructing a tandem dimeric form. The resulting bivalent form showed a broader neutralizing activity against the variants. The in vivo neutralizing efficacy of the bivalent synthetic antibody was confirmed using a human ACE2-expressing mouse model that significantly alleviated viral titer and lung infection. The present approach can be used to develop a synthetic antibody showing a broader neutralizing activity against a multitude of SARS-CoV-2 variants.

引用

页数：11

共 60 条

[1] SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies
Barnes, Christopher O.
Jette, Claudia A.
Abernathy, Morgan E.
Dam, Kim-Marie A.
Esswein, Shannon R.
Gristick, Harry B.
Malyutin, Andrey G.
Sharaf, Naima G.
Huey-Tubman, Kathryn E.
Lee, Yu E.
Robbiani, Davide F.
Nussenzweig, Michel C.
West, Anthony P., Jr.
Bjorkman, Pamela J.
[J]. NATURE, 2020, 588 (7839) : 682 - +
[2] Barnes CO, 2020, CELL, V182, P828, DOI [10.1016/j.cell.2020.06.025, 10.1101/2020.05.28.121533]
[3] Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies
Baum, Alina
Fulton, Benjamin O.
Wloga, Elzbieta
Copin, Richard
Pascal, Kristen E.
Russo, Vincenzo
Giordano, Stephanie
Lanza, Kathryn
Negron, Nicole
Ni, Min
Wei, Yi
Atwal, Gurinder S.
Murphy, Andrew J.
Stahl, Neil
Yancopoulos, George D.
Kyratsous, Christos A.
[J]. SCIENCE, 2020, 369 (6506) : 1014 - +
[4] Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2
Bracken, Colton J.
Lim, Shion A.
Solomon, Paige
Rettko, Nicholas J.
Nguyen, Duy P.
Zha, Beth Shoshana
Schaefer, Kaitlin
Byrnes, James R.
Zhou, Jie
Lui, Irene
Liu, Jia
Pance, Katarina
Zhou, Xin X.
Leung, Kevin K.
Wells, James A.
[J]. NATURE CHEMICAL BIOLOGY, 2021, 17 (01) : 113 - 121
[5] Cardiff Robert D, 2014, Cold Spring Harb Protoc, V2014, P655, DOI 10.1101/pdb.prot073411
[6] Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies
Chen, Rita E.
Zhang, Xianwen
Case, James Brett
Winkler, Emma S.
Liu, Yang
VanBlargan, Laura A.
Liu, Jianying
Errico, John M.
Xie, Xuping
Suryadevara, Naveenchandra
Gilchuk, Pavlo
Zost, Seth J.
Tahan, Stephen
Droit, Lindsay
Turner, Jackson S.
Kim, Wooseob
Schmitz, Aaron J.
Thapa, Mahima
Wang, David
Boon, Adrianus C. M.
Presti, Rachel M.
O'Halloran, Jane A.
Kim, Alfred H. J.
Deepak, Parakkal
Pinto, Dora
Fremont, Daved H.
Crowe, James E., Jr.
Corti, Davide
Virgin, Herbert W.
Ellebedy, Ali H.
Shi, Pei-Yong
Diamond, Michael S.
[J]. NATURE MEDICINE, 2021, 27 (04) : 717 - 726
[7] An ultrapotent RBD-targeted biparatopic nanobody neutralizes broad SARS-CoV-2 variants
Chi, Xiaojing
Zhang, Xinhui
Pan, Shengnan
Yu, Yanying
Shi, Yujin
Lin, Tianli
Duan, Huarui
Liu, Xiuying
Chen, Wenfang
Yang, Xuehua
Chen, Lan
Dong, Xiaoqian
Ren, Lili
Ding, Qiang
Wang, Jianwei
Yang, Wei
[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY, 2022, 7 (01)
[8] Features and development of Coot
Emsley, P.
Lohkamp, B.
Scott, W. G.
Cowtan, K.
[J]. ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 2010, 66 : 486 - 501
[9] Garcia-Beltran WF, 2021, CELL, V184, P2372, DOI [10.1101/2021.02.14.21251704, 10.1016/j.cell.2021.03.013, 10.1016/j.cell.2021.04.006]
[10] Gobeil SMC, 2021, SCIENCE, V373, P641, DOI [10.1126/science.abi6226, 10.1101/2021.03.11.435037]

← 1 2 3 4 5 6 →