ACE2 Receptor Decoy is a Potent Prophylactic and Therapeutic for SARS-CoV-2

The emergence of SARS-CoV-2 variants with highly mutated spike proteins has presented a major obstacle to the use of monoclonal antibodies for the prevention of SARS-CoV-2 infection and treatment of COVID-19. Better prophylactic and therapeutics for current and future variants are needed. We show that a high affinity receptor decoy protein in which a modified ectodomain of human ACE2 is fused a single domain of an immunoglobulin heavy chain Fc region dramatically suppressed virus loads in mice upon challenge with high dose of parental SARS-CoV-2 or Omicron variants BA.1 and BA.2 and potently suppressed virus replication when administered post-infection. The approach offers protection that is broader than monoclonal antibodies that are likely to be evaded by the continued evolution of the viral spike protein. ### Competing Interest Statement The authors have declared no competing interest.