Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity

Yuanmei Zhu; Danwei Yu; Hongxia Yan; Huihui Chong; Yuxian He

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.26.009233 doi: bioRxiv preprint 8 increased helix contents with a T m of 65 o C. Next, we assessed the helical binding stability of 143 the inhibitors with the two target mimic peptides, SARS2NP and SARS1NP. As shown in Fig 158 We next sought to determine the antiviral functions of the IPB01 and IPB02 peptides. Firstly, 159 their inhibitory activities on S protein-mediated cell-cell fusion were examined by the 160 DSP-based cell fusion assay as described above. As shown in Fig. 6A and Table 1 (Table 1) . As expected, IPB01 and IPB02 had no inhibitory activity against a 168 control virus (VSV-G), indicating their antiviral specificities. Therefore, we conclude that 169 IPB02 is a highly potent fusion inhibitor of SARS-CoV-2 and SARS-CoV. Differently, IPB08 was a C-terminally truncated inhibitor with IPB02 as a template, but its 183 antiviral function was markedly impaired, underscoring the roles of C-terminal residues in 184 IPB02. On the basis of the results above, it was expected that IPB09 with two terminal 185 truncations was antivirally inactive. Indeed, the CD data suggested that both the N-and 186 author/funder. All rights reserved. No reuse allowed without permission.