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

According to sequence alignment, the S2 subunits of SARS-CoV-2 and 198 SARS-CoV are highly conserved, with 92.6% and 100% overall homology in HR1 through a weak salt bridge 3.7 Ã… in distance. In SARS-CoV-2, E918 is mutated to 212 D936 and binds to R1185 in the HR2 domain through a salt bridge 2.7 Ã… in distance 213 (Fig. 3c) . In SARS-CoV, K929 in HR1 binds to E1163 in HR2 through a salt bridge 214 3.2 Ã… in distance, while T925 is not involved in the interaction. However, when T925 215 was mutated to S943, it could bind to E1182 in the HR2 domain with a hydrogen 216 bond 2.6 Ã… in distance, and K947 could also bind to E1182 through a salt bridge 3.0 217 Ã… in distance (Fig. 3d) . These results suggested that the multiple replacements in the 218 HR1 domain of emerging SARS-CoV-2 virus could enhance the interactions between 219 HR1 and HR2 domain to further stabilize the 6-HB structure, which may lead to 220 increased infectivity of the virus. 221 author/funder. All rights reserved. No reuse allowed without permission.