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The copyright holder for this preprint (which was not peer-reviewed) is the .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 EK with IC 50 ranging from 237.0 to 279.6 nM ( Fig. 5f -h). As control, the 278 EK1-scrambled peptide showed no inhibitory activity with concentration up to 5 μM 279 in all those coronavirus cell-cell fusion assays ( Fig. 5a-h) . 280 We also assessed the antiviral activity of EK1C4 on PsV infection by divergent The copyright holder for this preprint (which was not peer-reviewed) is the .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 (CC 50 ) was beyond 5 μM, which is the highest detection concentration of EK1C4 (Fig. 306 S3). Therefore, the selectivity index (SI=CC 50 /IC 50 ) of EK1C4 is >136, suggesting 307 that EK1C4 is a promising SARS-CoV-2 fusion inhibitor with little, or even no, toxic 308 effect in vitro. Further, we explored the potent antiviral mechanism of EK1C4 and 309 found that the complexes of EK1C4/SARS-2HR1, EK1C4/MERS-HR1, and 310 EK1C4/SARS-2HR1 harbor higher stability and increased Tm values than those of the 311 complexes formed by EK1 and HR1s (Fig. S4) . These results suggested that increased 312 antiviral activity of EK1C4 should be related its increased binding affinity with HR1, 313 but their detailed interactions require further studies. The copyright holder for this preprint (which was not peer-reviewed) is the .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