Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig

Changhai Lei; Wenyan Fu; Kewen Qian; Tian Li; Sheng Zhang; Min Ding; Shi Hu

After we identified that ACE2 fusion proteins binds to the RBDs with high affinity, The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.02.01.929976 doi: bioRxiv preprint ~ 5 ~ soluble proteins to extend plasma residence time, improve in vivo efficacy, and gain immunoreactive functions, has been widely used in modern biopharmaceuticals. For example, new long-acting forms of both recombinant coagulation factors rFVIII-Fc and rFIX-Fc were recently approved for clinical treatments of hemophilia A and B that require less frequent infusions 15, 16 . And the TNF receptor fusion protein has been use in clinic for decades 17 . Unlike the blood resident enzymes of coagulation factors, full-length endogenous ACE2 is a transmembrane protein anchored to the cell surface and that ACE2 activities are, in fact, present at very low levels in systemic circulation [18] [19] [20] . Therefore, one safety concern of the ACE2 fusion protein is that they may have systemic cardiovascular side-effect. Interestingly, one recently report shows that treatment of murine ACE2 fusion proteins in mice show no evidence of side-effect 12 . Moreover, our preliminary studies showed that the neutralization effect remained efficient when two active-site histidines of ACE2 were modified to asparagine.