tetano
Editor, Senior Moderator
Elife
. 2026 May 18:14:RP108883.
doi: 10.7554/eLife.108883.
Redirection of SARS-CoV-2 to phagocytes by intranasal sACE2-Fc as a universal decoy confers complete prophylactic protection
Jingyi Wang[SUP] #[/SUP][SUP] 1 [/SUP], Jiangchuan Li[SUP] #[/SUP][SUP] 1 [/SUP], Alex W H Chin[SUP] #[/SUP][SUP] 2 3 [/SUP], Bin Luo[SUP] 1 4 [/SUP], Junkang Wei[SUP] 1 [/SUP], Jiale Qiu[SUP] 1 [/SUP], Jianwei Ren[SUP] 1 4 [/SUP], Yin Xia[SUP] 1 [/SUP], Thomas Braun[SUP] 1 5 [/SUP], Leo L M Poon[SUP] 2 3 6 [/SUP], Bo Feng[SUP] 1 4 7 [/SUP]
Affiliations
The rapid evolution of SARS-CoV-2 and other respiratory RNA viruses limits the success of current vaccines and antibody-based therapies. Engineered decoy receptors based on soluble angiotensin-converting enzyme 2 (sACE2) offer promising alternatives but show limited clinical success. This study conducted functional and mechanistic analyses using an optimized sACE2 mutant fused to human IgG1 Fc (B5-D3) as a representative, revealing redirection of virus-decoy complexes from epithelial infection to lysosomal degradation in phagocytes beyond viral neutralization. Intranasal prophylactic delivery of B5-D3 confers complete protection in SARS-CoV-2-infected K18-hACE2 mice, regardless of age. Abrogation of Fc effector functions compromises antiviral protection, indicating that Fc-mediated uptake of virus-decoy complexes is critical. Transcriptomic analysis suggests that B5-D3 induces early immune activation in the lungs of infected mice. Bio-distribution and flow cytometry reveal selective targeting of airway phagocytes. In vitro assays confirm lysosomal degradation of virus-decoy complexes by macrophages without productive infection. These findings reveal a distinct antiviral mechanism via phagocytic clearance, supporting refined regimens for decoy treatments against SARS-CoV-2 and potentially other respiratory viruses.
Keywords: ACE2-Fc decoy; SARS-CoV-2; immunology; infectious disease; inflammation; intranasal prophylactics; macrophages; microbiology; viruses.
. 2026 May 18:14:RP108883.
doi: 10.7554/eLife.108883.
Redirection of SARS-CoV-2 to phagocytes by intranasal sACE2-Fc as a universal decoy confers complete prophylactic protection
Jingyi Wang[SUP] #[/SUP][SUP] 1 [/SUP], Jiangchuan Li[SUP] #[/SUP][SUP] 1 [/SUP], Alex W H Chin[SUP] #[/SUP][SUP] 2 3 [/SUP], Bin Luo[SUP] 1 4 [/SUP], Junkang Wei[SUP] 1 [/SUP], Jiale Qiu[SUP] 1 [/SUP], Jianwei Ren[SUP] 1 4 [/SUP], Yin Xia[SUP] 1 [/SUP], Thomas Braun[SUP] 1 5 [/SUP], Leo L M Poon[SUP] 2 3 6 [/SUP], Bo Feng[SUP] 1 4 7 [/SUP]
Affiliations
- PMID: 42149106
- DOI: 10.7554/eLife.108883
The rapid evolution of SARS-CoV-2 and other respiratory RNA viruses limits the success of current vaccines and antibody-based therapies. Engineered decoy receptors based on soluble angiotensin-converting enzyme 2 (sACE2) offer promising alternatives but show limited clinical success. This study conducted functional and mechanistic analyses using an optimized sACE2 mutant fused to human IgG1 Fc (B5-D3) as a representative, revealing redirection of virus-decoy complexes from epithelial infection to lysosomal degradation in phagocytes beyond viral neutralization. Intranasal prophylactic delivery of B5-D3 confers complete protection in SARS-CoV-2-infected K18-hACE2 mice, regardless of age. Abrogation of Fc effector functions compromises antiviral protection, indicating that Fc-mediated uptake of virus-decoy complexes is critical. Transcriptomic analysis suggests that B5-D3 induces early immune activation in the lungs of infected mice. Bio-distribution and flow cytometry reveal selective targeting of airway phagocytes. In vitro assays confirm lysosomal degradation of virus-decoy complexes by macrophages without productive infection. These findings reveal a distinct antiviral mechanism via phagocytic clearance, supporting refined regimens for decoy treatments against SARS-CoV-2 and potentially other respiratory viruses.
Keywords: ACE2-Fc decoy; SARS-CoV-2; immunology; infectious disease; inflammation; intranasal prophylactics; macrophages; microbiology; viruses.