7UHC
SARS-CoV-2 spike in complex with AHB2-2GS-SB175
Summary for 7UHC
| Entry DOI | 10.2210/pdb7uhc/pdb |
| EMDB information | 26512 |
| Descriptor | 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) |
| Functional Keywords | sars-cov-2, covid-19, spike glycoprotein, fusion protein, miniprotein inhibitor, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 6 |
| Total formula weight | 493035.98 |
| Authors | Park, Y.J.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2022-03-26, release date: 2022-06-08, Last modification date: 2024-10-30) |
| Primary citation | 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 Cited by 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: 35412328DOI: 10.1126/scitranslmed.abn1252 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
Download full validation report
