7KL9

Structure of the SARS-CoV-2 S 6P trimer in complex with the ACE2 protein decoy, CTC-445.2 (State 4)

7KL9 の概要

• エントリーDOI: 10.2210/pdb7kl9/pdb
• EMDBエントリー: 22916
• 分子名称: Spike glycoprotein, CTC-445.2 inhibitor, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: sars-cov-2, ace2 decoy, mini-protein, inhibitor, covid-19, antiviral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 476488.16

構造登録者

Barnes, C.O.,Bjorkman, P.J. (登録日: 2020-10-29, 公開日: 2020-11-11, 最終更新日: 2024-10-30)

主引用文献

Linsky, T.W.,Vergara, R.,Codina, N.,Nelson, J.W.,Walker, M.J.,Su, W.,Barnes, C.O.,Hsiang, T.Y.,Esser-Nobis, K.,Yu, K.,Reneer, Z.B.,Hou, Y.J.,Priya, T.,Mitsumoto, M.,Pong, A.,Lau, U.Y.,Mason, M.L.,Chen, J.,Chen, A.,Berrocal, T.,Peng, H.,Clairmont, N.S.,Castellanos, J.,Lin, Y.R.,Josephson-Day, A.,Baric, R.S.,Fuller, D.H.,Walkey, C.D.,Ross, T.M.,Swanson, R.,Bjorkman, P.J.,Gale Jr., M.,Blancas-Mejia, L.M.,Yen, H.L.,Silva, D.A.
De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2.
Science, 370:1208-1214, 2020

PubMed Abstract: We developed a de novo protein design strategy to swiftly engineer decoys for neutralizing pathogens that exploit extracellular host proteins to infect the cell. Our pipeline allowed the design, validation, and optimization of de novo human angiotensin-converting enzyme 2 (hACE2) decoys to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The best monovalent decoy, CTC-445.2, bound with low nanomolar affinity and high specificity to the receptor-binding domain (RBD) of the spike protein. Cryo-electron microscopy (cryo-EM) showed that the design is accurate and can simultaneously bind to all three RBDs of a single spike protein. Because the decoy replicates the spike protein target interface in hACE2, it is intrinsically resilient to viral mutational escape. A bivalent decoy, CTC-445.2d, showed ~10-fold improvement in binding. CTC-445.2d potently neutralized SARS-CoV-2 infection of cells in vitro, and a single intranasal prophylactic dose of decoy protected Syrian hamsters from a subsequent lethal SARS-CoV-2 challenge.

PubMed: 33154107
DOI: 10.1126/science.abe0075

実験手法

ELECTRON MICROSCOPY (4.1 Å)