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ACE2 receptor

Angiotensin-converting enzyme 2 — the cell-surface protein on lung, gut, heart, and blood-vessel cells that the SARS-CoV-2 spike protein binds to gain entry.

Edited by M. Callahan · Last reviewed 2026-05-10

How researchers study it

ACE2 was identified in 2000 as a homologue of the older ACE enzyme. Its role as a SARS-CoV receptor was established in 2003 with the original SARS coronavirus, and confirmed for SARS-CoV-2 in early 2020 (Hoffmann et al., Cell, 2020, PubMed 32142651). The interaction is direct: the spike protein's receptor-binding domain (RBD) makes contact with the peptidase domain of ACE2, and a host protease called TMPRSS2 cleaves spike to drive membrane fusion.

Tissue expression of ACE2 has been mapped extensively. The Human Protein Atlas and several independent studies show ACE2 in alveolar type II pneumocytes (lungs), enterocytes (small intestine), cardiomyocytes (heart), and vascular endothelial cells (Human Protein Atlas: ACE2). This distribution helps explain why COVID-19 affects multiple organ systems rather than only the lungs.

In its normal physiological role, ACE2 cleaves the peptide angiotensin II — a vasoconstrictor — into angiotensin-(1-7), which has vasodilatory and anti-inflammatory effects (Gheblawi et al., Circulation Research, 2020). When SARS-CoV-2 binds and internalizes ACE2, surface levels can fall, which some research groups have hypothesized may contribute to the inflammatory and cardiovascular features of severe COVID-19. This remains an active research area, not a settled mechanism.

Common misconceptions

"ACE2 is only in the lungs."It is found in many tissues — lung, gut, heart, kidney, vascular endothelium — which is why SARS-CoV-2 has effects beyond the respiratory tract.
"ACE2 was created to receive the virus."ACE2 is a normal human enzyme with a regulatory role in blood pressure that long predates any coronavirus. The virus exploits an existing host protein.
"Blocking ACE2 would cure COVID-19."ACE2 has essential physiological functions. Completely blocking it would create its own problems. Therapeutic strategies have instead focused on blocking the spike-ACE2 interaction itself.
WHAT THIS DOES NOT MEAN This entry describes ACE2 as a research target and host receptor. It is not a claim that any supplement, food, or product modulates ACE2 expression safely in humans, and it is not a diagnostic statement about any reader's ACE2 levels. Talk to a clinician about your individual health.
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SOURCES
  1. Hoffmann M et al. "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor." Cell, 2020. PubMed: 32142651
  2. Gheblawi M et al. "Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System." Circulation Research, 2020. PMC7164875
  3. Human Protein Atlas: ACE2 tissue expression. proteinatlas.org
Informational only · Not medical advice This entry describes a biological receptor and its role in published research. It does not diagnose, treat, cure, or prevent any disease. Medical decisions belong with a licensed clinician who knows your history.