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

As shown in Fig. 2C and 2D, the SARS-CoV S protein exhibited had no appreciable fusion 105 activity until the effector cells and target cells were cocultured for five or six hours; in sharp 106 contrast, the SARS-CoV-2 S protein mediated a rapid and robust cell fusion reaction, as 107 indicated by its fusion kinetic curves especially in 293T/ACE2 cells. SARS-CoV, SARS-CoV-2 has a HR1 sequence with nine amino acid substitutions, and of 113 them eight are located within the HR1 core site; whereas, two viruses share a fully identical 114 HR2 sequence (Fig. 3A) . In order to explore the mechanism underlying the highly active 115 fusion activity of the SARS-CoV-2 S protein, we synthesized two peptides corresponding to 116 the HR1 sequence and their secondary structures were determined by circular dichroism (CD) 117 spectroscopy. As shown in Fig. 3B , the HR1 peptide derived from SARS-CoV-2, designated 118 SARS2NP, showed a typical α-helical conformation with the helix contents of 66%, whereas 119 the HR1 peptide from SARS-CoV, designated SARS1NP, had α-helical contents of 41%. The 120 author/funder. All rights reserved. No reuse allowed without permission.