Protection Against SARS-CoV-2 Infection by ACE2 Decoy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves continuously under the humoral immune pressure. As the result, the many variants displaying immune evasion and antibody escape have emerged. An engineered angiotensin-converting enzyme 2 (ACE2) decoy which has higher affinity for the spike protein of SARS-CoV-2 could offer alternative way to neutralize SARS-CoV-2. In this study, we showed that ACE2 decoy capture spike proteins more readily than wild-type ACE2 by single particle cryo-EM. We also demonstrated that the ACE2 decoy retains neutralization activity against Omicron subvariants, which are resistant to antibodies. Furthermore, in SARS-CoV-2 infected rodents, inhalation of aerosolized ACE2 decoys was 20-fold efficient in its therapeutic effect than the intravenous administration. In addition, it is also demonstrated that ACE2 decoy has therapeutic effect for cynomolgus macaques. In this manuscript, in addition to these results, the structural analysis of spiked proteins by Cryo-EM will also be presented.