8TOS

ACE2-peptide 6 complex

8TOS の概要

• エントリーDOI: 10.2210/pdb8tos/pdb
• 関連するPDBエントリー: 8TOQ 8TOR
• 分子名称: Angiotensin-converting enzyme 2, Peptide 6, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: peptidase, enzyme, sars-cov2, angiotensin, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76128.01

構造登録者

Christie, M.,Payne, R. (登録日: 2023-08-03, 公開日: 2024-02-07, 最終更新日: 2024-10-23)

主引用文献

Bedding, M.J.,Franck, C.,Johansen-Leete, J.,Aggarwal, A.,Maxwell, J.W.C.,Patel, K.,Hawkins, P.M.E.,Low, J.K.K.,Siddiquee, R.,Sani, H.M.,Ford, D.J.,Turville, S.,Mackay, J.P.,Passioura, T.,Christie, M.,Payne, R.J.
Discovery of High Affinity Cyclic Peptide Ligands for Human ACE2 with SARS-CoV-2 Entry Inhibitory Activity.
Acs Chem.Biol., 19:141-152, 2024

PubMed Abstract: The development of effective antiviral compounds is essential for mitigating the effects of the COVID-19 pandemic. Entry of SARS-CoV-2 virions into host cells is mediated by the interaction between the viral spike (S) protein and membrane-bound angiotensin-converting enzyme 2 (ACE2) on the surface of epithelial cells. Inhibition of this viral protein-host protein interaction is an attractive avenue for the development of antiviral molecules with numerous spike-binding molecules generated to date. Herein, we describe an alternative approach to inhibit the spike-ACE2 interaction by targeting the spike-binding interface of human ACE2 via mRNA display. Two consecutive display selections were performed to direct cyclic peptide ligand binding toward the spike binding interface of ACE2. Through this process, potent cyclic peptide binders of human ACE2 (with affinities in the picomolar to nanomolar range) were identified, two of which neutralized SARS-CoV-2 entry. This work demonstrates the potential of targeting ACE2 for the generation of anti-SARS-CoV-2 therapeutics as well as broad spectrum antivirals for the treatment of SARS-like betacoronavirus infection.

PubMed: 38085789
DOI: 10.1021/acschembio.3c00568

実験手法

X-RAY DIFFRACTION (2.35 Å)