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

Furthermore, we synthesized a peptide containing the HR2 sequence, termed IPB01, and its 123 interactions with the two HR1 peptides were analyzed by CD spectroscopy. As shown in Fig. 124 3D and E, both the SARS2NP and SARS1NP interacted with IPB01 to form complexes with 125 typical α-helical structures, having the T m values of 75 and 68 o C, respectively. In comparison, 126 the complex formed by SARS2NP and IPB01 was much more stable than the complex 127 between the SARS1NP and IPB01 peptides. Taken together, these results suggested that 128 SARS-CoV-2 might evolve an increased interaction between the HR1 and HR2 domains in 129 the S2 fusion protein thus critically determining its high fusogenic activity. properties of the inhibitors in the absence or presence of a target mimic HR1 peptide. As 140 shown in Fig. 4A and 4B, the unconjugated IPB01 alone was largely in a random structure 141 and its T m value could not be defined. By contrast, the lipopeptide IPB02 displayed markedly 142 author/funder. All rights reserved. No reuse allowed without permission.