6LXT
Structure of post fusion core of 2019-nCoV S2 subunit
Summary for 6LXT
| Entry DOI | 10.2210/pdb6lxt/pdb |
| Descriptor | Spike protein S2, Spike protein S2, TETRAETHYLENE GLYCOL, ZINC ION (3 entities in total) |
| Functional Keywords | 2019-ncov, hr1 and hr2 domain, virus, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) More |
| Total number of polymer chains | 6 |
| Total formula weight | 84658.01 |
| Authors | |
| Primary citation | Xia, S.,Liu, M.,Wang, C.,Xu, W.,Lan, Q.,Feng, S.,Qi, F.,Bao, L.,Du, L.,Liu, S.,Qin, C.,Sun, F.,Shi, Z.,Zhu, Y.,Jiang, S.,Lu, L. Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res., 30:343-355, 2020 Cited by PubMed Abstract: The recent outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 infection in Wuhan, China has posed a serious threat to global public health. To develop specific anti-coronavirus therapeutics and prophylactics, the molecular mechanism that underlies viral infection must first be defined. Therefore, we herein established a SARS-CoV-2 spike (S) protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. We solved the X-ray crystal structure of six-helical bundle (6-HB) core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. We previously developed a pan-coronavirus fusion inhibitor, EK1, which targeted the HR1 domain and could inhibit infection by divergent human coronaviruses tested, including SARS-CoV and MERS-CoV. Here we generated a series of lipopeptides derived from EK1 and found that EK1C4 was the most potent fusion inhibitor against SARS-CoV-2 S protein-mediated membrane fusion and pseudovirus infection with IC50s of 1.3 and 15.8 nM, about 241- and 149-fold more potent than the original EK1 peptide, respectively. EK1C4 was also highly effective against membrane fusion and infection of other human coronavirus pseudoviruses tested, including SARS-CoV and MERS-CoV, as well as SARSr-CoVs, and potently inhibited the replication of 5 live human coronaviruses examined, including SARS-CoV-2. Intranasal application of EK1C4 before or after challenge with HCoV-OC43 protected mice from infection, suggesting that EK1C4 could be used for prevention and treatment of infection by the currently circulating SARS-CoV-2 and other emerging SARSr-CoVs. PubMed: 32231345DOI: 10.1038/s41422-020-0305-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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