angiotensin I converting enzyme 2

Overview

Angiotensin I converting enzyme 2 (ACE2) is a membrane-associated protein best known as a key regulator of the renin–angiotensin system and as the cellular receptor used by SARS-CoV-2 for entry into host cells. In normal physiology, ACE2 counterbalances angiotensin-converting enzyme activity by processing angiotensin Peptides, thereby contributing to vascular, renal, and inflammatory homeostasis. Because of this dual role in human biology and viral attachment, ACE2 has become an important target in cardiovascular, renal, and infectious disease research.

Structurally, ACE2 is of major interest because its extracellular domain directly engages the receptor-binding domain of the SARS-CoV-2 spike protein. Variants and mutations in the viral spike can alter this interaction, affecting infectivity and immune escape. ACE2 is also studied in disease-associated expression analyses, including kidney disorders, where altered ACE2 expression may reflect changes in tissue injury, inflammation, or immune infiltration.

Recent Publications Focus

Below is a summary of the newest research publications targeting angiotensin I converting enzyme 2 (sorted by publication date).

Recent studies have continued to examine angiotensin I converting enzyme 2 (ACE2) in both disease biomarker and viral-entry contexts. In a case-control study of mid-pregnancy plasma proteins, ACE2 was among the cardiovascular proteins most notably altered in women who later developed term preeclampsia, alongside B-type natriuretic peptide, suggesting involvement of cardiovascular dysregulation in adverse pregnancy outcomes. In a separate bioinformatics analysis of IgA nephropathy, ACE2 was identified as one of six pyroptosis-related hub genes with high diagnostic accuracy, and its differential expression was validated in human kidney tissues and serum samples.

Several publications focused on ACE2 as the host receptor for SARS-CoV-2 spike binding. One study combined machine learning with iterative high-throughput experimentation to predict receptor-binding domain variants with altered binding to human ACE2, using public datasets and experimental refinement to improve model performance for variant prioritization. Another used ligand-based pharmacophore modeling and structure-based virtual screening to identify small-molecule inhibitors of the spike-ACE2 interaction, with in vitro assays confirming that two compounds inhibited spike-ACE2 binding with low cytotoxicity. A related bottom-up liposomal virus-like particle platform incorporated SARS-CoV-2 spike ectodomain conjugates into liposomes and showed enhanced ACE2 plate-binding, with binding reduced by Congo Red and a neutralizing anti-spike antibody.

Additional work explored alternative strategies to block spike-ACE2 engagement. Deep mutational learning was used to map serum polyclonal antibody escape across diverse receptor-binding domain variant libraries, building on prior ACE2-binding studies to better understand mutational effects on viral interaction and immune escape. Separately, an abiotic antibody mimic based on hydrogel polymer nanoparticles was engineered to target the spike receptor-binding domain; its binding epitopes overlapped with ACE2-binding sites, enabling competitive inhibition of spike RBD-ACE2 interactions and supporting biomolecule-free detection platforms for SARS-CoV-2 antigens and pseudoviruses.

Target PMIDs

[PMID 41478048]
[PMID 42030951]
[PMID 42135973]
[PMID 42160665]
[PMID 42174382]
[PMID 42308256]
[PMID 42409921]