BCE2 Antibody

Definition and Functional Role of ACE2 Antibodies

ACE2 antibodies are immunoglobulins designed to bind to the ACE2 receptor, a membrane protein expressed in human tissues such as the lungs, heart, and intestines. ACE2 serves as the primary entry receptor for coronaviruses, including SARS-CoV-2, SARS-CoV, and HCoV-NL63. These antibodies block viral attachment by interfering with the interaction between the viral spike protein and ACE2 .

Monoclonal Antibody 3E8

Study: A human monoclonal antibody (3E8) demonstrated broad-spectrum neutralization against ACE2-dependent coronaviruses, including SARS-CoV-2 variants (B.1.1.7, B.1.351), SARS-CoV, and HCoV-NL63 .

• Efficacy:

  • In vitro: IC₅₀ = 0.04 nM against live SARS-CoV-2 in Vero E6 cells.

  • In vivo: Prophylactic administration reduced lung viral loads by 40-fold in a COVID-19 mouse model .

• Epitope Mapping: Cryo-EM revealed binding to ACE2 residues critical for viral spike interaction, partially overlapping with the RBD interface .

Bispecific Antibody Formats

Study: Bispecific antibodies (bsAbs) combining ACE2-targeting and spike-neutralizing domains enhanced neutralization breadth against SARS-CoV-2 variants and MERS-CoV .

• Design: "Knob-into-Hole" and "IgG-scFv" technologies.

• Results:

  Format	Neutralization Breadth	Potency (IC₅₀)
  ACE2 × SARS-CoV-2 bsAb	SARS-CoV-2 variants, SARS-CoV	0.02–0.15 nM
  ACE2 × MERS-CoV bsAb	MERS-CoV, SARS-CoV-2 (cross-reactive)	0.1–0.3 nM

Bimodular Fusion Proteins

Study: An ACE2-P18F3 fusion protein redirected endogenous anti-Epstein-Barr virus antibodies toward SARS-CoV-2, enhancing phagocytosis and viral clearance .

• Advantage: Leverages pre-existing anti-P18 antibodies in >98% of adults.

• Outcome: Reduced viral titers in pseudovirus assays by 90% .

Comparative Analysis of ACE2 Antibodies vs. RBD-Targeting Antibodies

Future Directions

• Multispecific Antibodies: Combining ACE2 targeting with anti-inflammatory domains (e.g., IL-6 blockers) to address cytokine storms.

• Universal Coronaviridae Vaccines: Epitopes identified on ACE2 could inform pan-coronavirus vaccine design .