ArticleProceedings of the National Academy of Sciences of the United States of America2020
Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.
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Who cites it
182 citing papers in PubMed, 1 synthesis or guideline pooled it, 261 citations in OpenAlex.
- SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19.The Cochrane database of systematic reviews · 2022Pooled it
- Trial
- A machine learning method for calculating highly localized protein stabilities.Nature communications · 2026Article
- ACE2-PNA conjugates exploit viral endocytosis for targeted intracellular delivery and exhibit dual antiviral efficacy against SARS-CoV-2.Molecular biomedicine · 2026Article
- Production of mannosylated hrsACE2 by baculovirus expression system; the way to remove and redirect SARS-CoV-2 viral particles to macrophages.Biotechnology letters · 2026Article
- A receptor-Fc based SFV replicon Trim-Away platform for targeted viral protein degradation.Virology journal · 2026Article
- Article
- Multifunctional ACE2-nanobody fusion design for pan-specific neutralization and cardiovascular protection in SARS coronavirus infection.Antimicrobial agents and chemotherapy · 2026Article
- Optimized ACE2-Fc fusion proteins with picomolar neutralization activity against highly evolved SARS-CoV-2 variants.Protein science : a publication of the Protein Society · 2026Article
- Viral receptors as host-pathogen control nodes linking entry, signalling, and system-level pathogenesis.FEMS microbiology reviews · 2026Review
- Development of ACE2-tropic-betacoronavirus therapeutics for future pandemic preparedness.Nature communications · 2025Article
- Systems biology and microbiome innovations for personalized diabetic retinopathy management.NPJ systems biology and applications · 2025Review
- Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist.Communications biology · 2025Article
- Rational design of a covalent ACE2 decoy receptor that broadly neutralizes SARS-CoV-2 variants.Protein science : a publication of the Protein Society · 2025Article
- A combinatorial and computational Tandem approach towards a universal therapeutics against ACE2-mediated coronavirus infections.iScience · 2025Article
- Article
- Angiotensin-converting enzyme 2 and hepatic SARS-CoV-2 infection: Regulation, association, and therapeutic implications.World journal of gastroenterology · 2025Article
- Directed Evolution of a Plant Immune Receptor for Broad Spectrum Effector Recognition.bioRxiv : the preprint server for biology · 2025Article
- ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture.Science advances · 2025Article
122 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
An essential mechanism for severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). Here, we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. These optimized receptor traps tightly bind the receptor binding domain (RBD) of the viral spike protein and prevent entry into host cells. We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. These designed receptor variants were affinity matured an additional 14-fold by random mutagenesis and selection using yeast surface display. The highest-affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. With the addition of the natural ACE2 collectrin domain and fusion to a human immunoglobulin crystallizable fragment (Fc) domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2-pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50s) in the 10- to 100-ng/mL range. Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-using coronaviruses, with the key advantage that viral resistance would also likely impair viral entry. Moreover, such traps can be predesigned for viruses with known entry receptors for faster therapeutic response without the need for neutralizing antibodies isolated from convalescent patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.