5ZUV
Crystal Structure of the Human Coronavirus 229E HR1 motif in complex with pan-CoVs inhibitor EK1
Summary for 5ZUV
| Entry DOI | 10.2210/pdb5zuv/pdb |
| Descriptor | Spike glycoprotein,Spike glycoprotein,inhibitor EK1, CHLORIDE ION (3 entities in total) |
| Functional Keywords | human coronavirus 229e, spike protein, s2 domain, hr1 motif, pan-coronavirus, viral protein, inhibitor |
| Biological source | Human coronavirus 229E (HCoV-229E) More |
| Total number of polymer chains | 3 |
| Total formula weight | 44141.94 |
| Authors | Yan, L.,Yang, B.,Wilson, I.A. (deposition date: 2018-05-08, release date: 2019-04-10, Last modification date: 2023-11-22) |
| Primary citation | 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 Cited by 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: 30989115DOI: 10.1126/sciadv.aav4580 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.21 Å) |
Structure validation
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