8P99
SARS-CoV-2 S-protein:D614G mutant in 1-up conformation
Summary for 8P99
| Entry DOI | 10.2210/pdb8p99/pdb |
| EMDB information | 17576 |
| Descriptor | Spike protein S1,Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | spike, sars cov-2, inhibitor, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 More |
| Total number of polymer chains | 3 |
| Total formula weight | 432265.33 |
| Authors | Adhav, A.,Forcada-Nadal, A.,Marco-Marin, C.,Lopez-Redondo, M.L.,Llacer, J.L. (deposition date: 2023-06-05, release date: 2023-09-27, Last modification date: 2024-11-13) |
| Primary citation | Gargantilla, M.,Frances, C.,Adhav, A.,Forcada-Nadal, A.,Martinez-Gualda, B.,Marti-Mari, O.,Lopez-Redondo, M.L.,Melero, R.,Marco-Marin, C.,Gougeard, N.,Espinosa, C.,Rubio-Del-Campo, A.,Ruiz-Partida, R.,Hernandez-Sierra, M.D.P.,Villamayor-Belinchon, L.,Bravo, J.,Llacer, J.L.,Marina, A.,Rubio, V.,San-Felix, A.,Geller, R.,Perez-Perez, M.J. C-2 Thiophenyl Tryptophan Trimers Inhibit Cellular Entry of SARS-CoV-2 through Interaction with the Viral Spike (S) Protein. J.Med.Chem., 66:10432-10457, 2023 Cited by PubMed Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, by infecting cells via the interaction of its spike protein (S) with the primary cell receptor angiotensin-converting enzyme (ACE2). To search for inhibitors of this key step in viral infection, we screened an in-house library of multivalent tryptophan derivatives. Using VSV-S pseudoparticles, we identified compound as a potent entry inhibitor lacking cellular toxicity. Chemical optimization of rendered compounds and , which also potently inhibited genuine SARS-CoV-2 cell entry. Thermofluor and microscale thermophoresis studies revealed their binding to S and to its isolated receptor binding domain (RBD), interfering with the interaction with ACE2. High-resolution cryoelectron microscopy structure of S, free or bound to , shed light on cell entry inhibition mechanisms by these compounds. Overall, this work identifies and characterizes a new class of SARS-CoV-2 entry inhibitors with clear potential for preventing and/or fighting COVID-19. PubMed: 37471688DOI: 10.1021/acs.jmedchem.3c00576 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
Download full validation report
