7C53

Crystal Structure of SARS-CoV-2 HR1 motif in complex with pan-CoVs inhibitor EK1

7C53 の概要

• エントリーDOI: 10.2210/pdb7c53/pdb
• 分子名称: Spike protein S2',pan-CoVs inhibitor EK1, CALCIUM ION (3 entities in total)
• 機能のキーワード: sars-cov-2 hr1, pan-covs inhibitor, ek1 peptide, virus, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 70040.53

構造登録者

Zhu, Y.,Yang, X.,Sun, F. (登録日: 2020-05-19, 公開日: 2021-05-19, 最終更新日: 2023-11-29)

主引用文献

Xia, S.,Lan, Q.,Zhu, Y.,Wang, C.,Xu, W.,Li, Y.,Wang, L.,Jiao, F.,Zhou, J.,Hua, C.,Wang, Q.,Cai, X.,Wu, Y.,Gao, J.,Liu, H.,Sun, G.,Munch, J.,Kirchhoff, F.,Yuan, Z.,Xie, Y.,Sun, F.,Jiang, S.,Lu, L.
Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation.
Signal Transduct Target Ther, 6:288-288, 2021

PubMed Abstract: The COVID-19 pandemic poses a global threat to public health and economy. The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines. In this study, we identified that EK1 and cholesterol-coupled derivative of EK1, EK1C4, as pan-CoV fusion inhibitors, exhibit potent antiviral activity against SARS-CoV-2 infection in both lung- and intestine-derived cell lines (Calu-3 and Caco2, respectively). They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7 (Alpha) and B.1.1.248 (Gamma) as well as those with mutations in S protein, including N417T, E484K, N501Y, and D614G, which are common in South African and Brazilian variants. Crystal structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral activity. Nasal administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal tissues. EK1 showed good safety profiles in various animal models, supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants.

PubMed: 34326308
DOI: 10.1038/s41392-021-00712-2

実験手法

X-RAY DIFFRACTION (2.278 Å)