8P99

SARS-CoV-2 S-protein:D614G mutant in 1-up conformation

8P99 の概要

• エントリーDOI: 10.2210/pdb8p99/pdb
• EMDBエントリー: 17576
• 分子名称: 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)
• 機能のキーワード: spike, sars cov-2, inhibitor, 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: 3
• 化学式量合計: 432265.33

構造登録者

Adhav, A.,Forcada-Nadal, A.,Marco-Marin, C.,Lopez-Redondo, M.L.,Llacer, J.L. (登録日: 2023-06-05, 公開日: 2023-09-27, 最終更新日: 2024-11-13)

主引用文献

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

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: 37471688
DOI: 10.1021/acs.jmedchem.3c00576

実験手法

ELECTRON MICROSCOPY (3.4 Å)