A pan-coronavirus fusion inhibitor targeting the HR1 domain of human coronavirus spike

Xia, Shuai; Yan, Lei; Xu, Wei; Agrawal, Anurodh Shankar; Algaissi, Abdullah; Tseng, Chien-Te K.; Wang, Qian; Du, Lanying; Tan, Wenjie; Wilson, Ian A.; Jiang, Shibo; Yang, Bei; Lu, Lu

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/ content/full/5/4/eaav4580/DC1 Fig. S1 . Interaction between HCoV HR1 and HR2 regions in HCoV S proteins. Fig. S2 . Identity and similarity in spike protein sequences of SARS-CoV and SL-CoVs and the effect of EK1 on HCoV S protein-mediated cell fusion and virus-cell fusion, as well as the viral loads and histopathological changes in brains of HCoV-infected mice. Fig. S3 . In vivo safety of EK1 through intranasal administration. Fig. S4 . Structural comparison between the HR1-EK1 6-HB bundles and cognate HR1-HR2 6-HB bundles reveals that the EK1 peptide binds to the triple-helix HR1 core of different HCoVs in a similar manner to that of the native HR2 of the corresponding HCoV. Fig. S5 . The EK1 peptide forms 6-helical bundle structures with the HR1 motifs from OC43, HKU1, and NL63. Fig. S6 . Interactions between the HR1 and HR2 motifs of MERS and 229E. Fig. S7 . Key residues at critical positions endow EK1 and OC43-HR2 with pan-CoV activity. Table S1 . Inhibitory activity of peptides on multiple cell-cell fusion assays. Table S2 . Solubility and fusion inhibitory activities of different peptides. Table S3 . Data collection and structural refinement statistics.