Key result
Intranasal ACE2.1mb receptor decoy reduces SARS-CoV-2 lung viral loads ~26,500-fold in mice.
Why the study?
The emergence of SARS-CoV-2 variants with highly mutated spike proteins has limited the effectiveness of monoclonal antibodies for prevention and treatment of infection.
Does a high affinity ACE2 receptor decoy protein suppress virus loads in mice challenged with SARS-CoV-2?
Does a high affinity ACE2 receptor decoy protein suppress virus loads in mice challenged with SARS-CoV-2?
A modified ACE2 receptor decoy protein effectively suppresses SARS-CoV-2 viral loads and replication in mice, offering a potential strategy against emerging variants.
Supports ACE2 decoy advancement to human trials; leaves open clinical translation, safety, and efficacy.
The emergence of SARS-CoV-2 variants with highly mutated spike proteins has presented an obstacle to the use of monoclonal antibodies for the prevention and treatment of SARS-CoV-2 infection. We show that a high affinity receptor decoy protein in which a modified ACE2 ectodomain is fused to a single domain of an immunoglobulin heavy chain Fc region dramatically suppressed virus loads in mice upon challenge with a high dose of parental SARS-CoV-2 or Omicron variants. The decoy also potently suppressed virus replication when administered shortly post-infection. The decoy approach offers protection against the current viral variants and, potentially, against SARS-CoV-2 variants that may emerge with the continued evolution of the spike protein or novel viruses that use ACE2 for virus entry.
No takes yet. Share an insight, caveat, or question.
Tada et al. (2023) studied SARS-CoV-2 infection. ACE2.1mb (high affinity ACE2 receptor decoy) vs. Mock, sACE2, ACE2.mb, or monoclonal antibodies (REGN-COV2, LY-CoV1404) was evaluated on Viral RNA load in the lung at 3 days post-infection (26,500-fold decrease). Intranasal administration of the high affinity ACE2.1mb receptor decoy suppressed SARS-CoV-2 viral loads in the lungs of mice by 26,500-fold when given prophylactically or shortly after infection.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: