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.

Focus of Latest Publications

Recent studies have used ACE2 primarily as a molecular target in SARS-CoV-2 interaction research and as a biomarker in disease profiling.

One publication on deep mutational learning and serum polyclonal antibody escape to SARS-CoV-2 variants used deep mutational scanning and related computational learning approaches to examine how single-position mutations in the spike receptor-binding domain affect ACE2 binding and neutralizing antibody recognition. The study context emphasizes that ACE2-binding sites are central to identifying mutations that drive immune escape, linking receptor engagement with antibody evasion. This type of work helps map the functional constraints on the viral RBD and clarifies which substitutions preserve or alter ACE2 affinity.

A second study focused on the SARS-CoV-2 spike protein–ACE2 receptor interaction as a therapeutic target. Using ligand-based pharmacophore modeling and structure-based virtual screening, the investigators sought potential agents that could interfere with spike–ACE2 binding. The study combined computational screening with molecular docking and molecular dynamics simulations to prioritize candidate compounds from the MolPort database. In this context, ACE2 served as the host receptor component of the target interface, and the goal was to identify molecules that might disrupt viral attachment.

A third publication examined pyroptosis-related hub genes in IgA nephropathy using bioinformatics analysis of GEO-derived expression data, including GSE99339. ACE2 emerged among six hub genes with high diagnostic accuracy for distinguishing IgA nephropathy samples from normal controls, alongside BHLHE40, JUN, CEBPB, IL1B, and CD14. The study used limma, LASSO regression, and SVM algorithms to identify and validate these genes. Although this work was not focused on ACE2 as a viral receptor, it supports the relevance of ACE2 in renal disease biology and inflammatory pathways, potentially intersecting with immune-cell processes involving macrophage activity and cytokine signaling such as Interleukin 1 beta.

A fourth study on engineering an abiotic antibody mimic for virus antigen targeting reported that key epitopes and residues involved in ATrp-NP7 binding coincide with ACE2-binding sites. This finding indicates that the engineered mimic recognizes regions overlapping the viral receptor interface, reinforcing the centrality of ACE2-contact residues in antigen detection and neutralization strategies. The study also used gold nanoparticles and lateral flow immunoassays, including Au@ATrp-NP7 and MLys-NP6, to support point-of-care testing applications.

Across these studies, ACE2 is consistently positioned as a biologically important receptor interface: in viral entry, in mutation-driven changes to spike binding, in therapeutic screening against spike attachment, and in disease-associated gene expression patterns in kidney pathology.

Key Publications

• NEWJun Bottom-Up Creation of Virus-like Particles via Post-Insertion of Protein-Lipid Conjugates. (ACS synthetic biology, 2026, PMID 42160665): "In an ACE2 plate-binding assay, Spike-modified liposomes showed higher binding ability than unmodified liposomes, and the binding was reduced by Congo Red, a reported inhibitor of the Spike-ACE2 interaction, and a neutralizing anti-Spike antibody."
• Jun Combining machine learning and iterative experiments to keep pace with emerging viral variants of concern. (PLoS computational biology, 2026, PMID 42308256): "Using public datasets, we trained predictive models for binding to human Angiotensin-converting enzyme 2 (ACE2), RBD expression, and antibody escape, and refined these models through iterative integration of experimental data focused on over 200 variants derived from wild-type (WT) and Omicron strains."
• Jun Dissecting serum polyclonal antibody escape to SARS-CoV-2 variants by deep mutational learning. (Cell reports methods, 2026, PMID 42030951): "Deep mutational scanning (DMS) has been extensively used to investigate how single-position mutations in the receptor-binding domain (RBD) affect binding of ACE2 and neutralizing antibodies, thus revealing mutations that drive immune escape."
• May Ligand-Based Pharmacophore Modeling and Structure-Based Virtual Screening for Identifying Potential Therapeutic Agents Targeting the SARS-CoV-2 Spike Protein-ACE2 Receptor Interaction. (ChemMedChem, 2026, PMID 42174382): "targeting the SARS-CoV-2 spike protein-ACE2 Receptor interaction."
• Dec Identification of pyroptosis-related hub genes and immune cell infiltration in IgA nephropathy via bioinformatics analysis. (Renal failure, 2026, PMID 42135973): "A total of 19 pyroptosis-related differentially expressed genes (nine up-regulated and 10 down-regulated) were identified, with six hub genes (BHLHE40, JUN, CEBPB, ACE2, IL1B, and CD14) showing high diagnostic accuracy for discriminating IgAN from normal samples (AUC > 0.9)."
• May Engineering an abiotic antibody mimic: Structural and molecular mechanisms for targeting, neutralizing, and point-of-care testing virus antigens. (Talanta, 2026, PMID 41478048): "...key epitopes and residues involved in ATrp-NP7 binding coincide with ACE2-binding sites..."