7UHC

SARS-CoV-2 spike in complex with AHB2-2GS-SB175

7UHC の概要

• エントリーDOI: 10.2210/pdb7uhc/pdb
• EMDBエントリー: 26512
• 分子名称: Spike glycoprotein, Multivalent miniprotein inhibitor AHB2-2GS-SB175, 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, covid-19, spike glycoprotein, fusion protein, miniprotein inhibitor, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 493035.98

構造登録者

Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (登録日: 2022-03-26, 公開日: 2022-06-08, 最終更新日: 2024-10-30)

主引用文献

Hunt, A.C.,Case, J.B.,Park, Y.J.,Cao, L.,Wu, K.,Walls, A.C.,Liu, Z.,Bowen, J.E.,Yeh, H.W.,Saini, S.,Helms, L.,Zhao, Y.T.,Hsiang, T.Y.,Starr, T.N.,Goreshnik, I.,Kozodoy, L.,Carter, L.,Ravichandran, R.,Green, L.B.,Matochko, W.L.,Thomson, C.A.,Vogeli, B.,Kruger, A.,VanBlargan, L.A.,Chen, R.E.,Ying, B.,Bailey, A.L.,Kafai, N.M.,Boyken, S.E.,Ljubetic, A.,Edman, N.,Ueda, G.,Chow, C.M.,Johnson, M.,Addetia, A.,Navarro, M.J.,Panpradist, N.,Gale Jr., M.,Freedman, B.S.,Bloom, J.D.,Ruohola-Baker, H.,Whelan, S.P.J.,Stewart, L.,Diamond, M.S.,Veesler, D.,Jewett, M.C.,Baker, D.
Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice.
Sci Transl Med, 14:eabn1252-eabn1252, 2022

PubMed Abstract: New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than the monoclonal antibodies used clinically for the treatment of COVID-19. TRI2-2 also conferred prophylactic and therapeutic protection against SARS-CoV-2 challenge when administered intranasally in mice. Designed miniprotein receptor mimics geometrically arrayed to match pathogen receptor binding sites could be a widely applicable antiviral therapeutic strategy with advantages over antibodies in greater resistance to viral escape and antigenic drift, and advantages over native receptor traps in lower chances of autoimmune responses.

PubMed: 35412328
DOI: 10.1126/scitranslmed.abn1252

実験手法

ELECTRON MICROSCOPY (3.1 Å)