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

As shown in Fig. S6 , high viral titer was detected in brains of all 5 mice in Pre-24 339 group and 4 out of 5 mice in Post-2 group, but was not detected in brain tissues of all 340 mice in Pre-0.5, Pre-2, Pre-4, and Post-0.5 groups, while only moderate level of viral 341 titer was detected in brain tissue in one of the 5 mice in Pre-12 group (Fig. S6 a and b) . Inducing the S1/S2 furin-recognition site could significantly increase the capacity of 371 SARS-CoV S protein to mediate cellular membrane surface infection 26 . Interestingly, 372 SARS-CoV-2 harbors the S1/S2 cleavage site in its S protein, but its specific role in S 373 protein-mediated membrane fusion and viral life-cycle remains to be further explored 374 (Fig. S7) . A recent report suggested that SARS-CoV-2 mainly used TMPRSS2 for 375 plasma membrane fusion; this means that the TMPRSS2 inhibitor might constitute an 376 option for blocking SARS-CoV-2 fusion with and entry into the host cell 27 .