Inhibition of SARS-CoV-2 infection (previously 2019-nCoV) by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion

Shuai Xia; Meiqin Liu; Chao Wang; Wei Xu; Qiaoshuai Lan; Siliang Feng; Feifei Qi; Linlin Bao; Lanying Du; Shuwen Liu; Chuan Qin; Fei Sun; Zhengli Shi; Yun Zhu; Shibo Jiang; Lu Lu

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.09.983247 doi: bioRxiv preprint Design and structure-activity relationship (SAR) analysis of lipopeptides with 222 remarkably improved fusion inhibitory activity 223 Previously, we found that peptide EK1 could disturb viral 6-HB formation and for EK1P, respectively (Fig. 4c) . Meanwhile, the EK1-scrambled peptide showed no 236 inhibitory activity with the concentration up to 5 μM (Fig. 4c) . These results strongly 237 suggest that lipidation of EK1 is a promising strategy to improve its fusion-inhibitory 238 activity against SARS-CoV-2 infection, especially, cholesterol-modification. 239 On the basis of the structure of EK1C, series of cholesteryl EK1 with multiple 240 linkers were constructed, where the glycine/serine-based linker, i.e., GSG, or 241 PEG-based spacer was employed between EK1 and the cholesterol moiety (Fig. 4d ).