5ZVM

Crystal Structure of the Human Coronavirus SARS HR1 motif in complex with pan-CoVs inhibitor EK1

5ZVM の概要

• エントリーDOI: 10.2210/pdb5zvm/pdb
• 関連するPDBエントリー: 5ZUV 5ZVK
• 分子名称: Spike glycoprotein, pan-CoV inhibitory peptide EK1 (2 entities in total)
• 機能のキーワード: sars, spike protein, s2 domain, hr1 motif, pan-coronavirus, viral protein-inhibitor complex, viral protein/inhibitor
• 由来する生物種: Human SARS coronavirus (SARS-CoV); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 40866.67

構造登録者

Yan, L.,Yang, B.,Wilson, I.A. (登録日: 2018-05-11, 公開日: 2019-04-10, 最終更新日: 2023-11-22)

主引用文献

Xia, S.,Yan, L.,Xu, W.,Agrawal, A.S.,Algaissi, A.,Tseng, C.K.,Wang, Q.,Du, L.,Tan, W.,Wilson, I.A.,Jiang, S.,Yang, B.,Lu, L.
A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike.
Sci Adv, 5:eaav4580-eaav4580, 2019

PubMed Abstract: Continuously emerging highly pathogenic human coronaviruses (HCoVs) remain a major threat to human health, as illustrated in past SARS-CoV and MERS-CoV outbreaks. The development of a drug with broad-spectrum HCoV inhibitory activity would address this urgent unmet medical need. Although previous studies have suggested that the HR1 of HCoV spike (S) protein is an important target site for inhibition against specific HCoVs, whether this conserved region could serve as a target for the development of broad-spectrum pan-CoV inhibitor remains controversial. Here, we found that peptide OC43-HR2P, derived from the HR2 domain of HCoV-OC43, exhibited broad fusion inhibitory activity against multiple HCoVs. EK1, the optimized form of OC43-HR2P, showed substantially improved pan-CoV fusion inhibitory activity and pharmaceutical properties. Crystal structures indicated that EK1 can form a stable six-helix bundle structure with both short α-HCoV and long β-HCoV HR1s, further supporting the role of HR1 region as a viable pan-CoV target site.

PubMed: 30989115
DOI: 10.1126/sciadv.aav4580

実験手法

X-RAY DIFFRACTION (3.3 Å)