ACE2 — concise summary for biologists
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Summary
ACE2 is the functional entry receptor for SARS‑CoV and SARS‑CoV‑2: the viral spike (S) receptor‑binding domain (RBD) engages the ACE2 peptidase domain, supported by structural and functional studies that show a conserved binding mode and, for SARS‑CoV‑2, generally higher RBD affinity for human ACE2. Full‑length ACE2 structures (complexed with the B0AT1 transporter) define ACE2 dimerization and the molecular interface for RBD recognition.
Spike activation by host proteases is required for ACE2‑dependent entry: TMPRSS2 primes S at the cell surface, and furin pre‑cleavage of SARS‑CoV‑2 S can reduce dependence on target‑cell proteases; pharmacologic inhibition of these proteases blocks entry in vitro and is a candidate antiviral strategy,.
ACE2 expression is cell‑type specific and consistent with respiratory, intestinal and vascular tropism: ACE2 is expressed in lung alveolar epithelium, small intestinal enterocytes and vascular endothelium, which may contribute to multisystem manifestations of COVID‑19 and to routes of infection,. Viral engagement and downregulation of ACE2 can perturb the renin–angiotensin system and worsen lung injury, linking receptor usage to pathogenesis.
Implications: structural and biochemical mapping of the ACE2–S interface informs therapeutic design (neutralizing antibodies, soluble ACE2 decoys) and helps explain species/host‑range differences; targeting protease activation (e.g., TMPRSS2/furin) is an orthogonal intervention approach,,.
This summary was generated by summarizing the top 50 most cited paper abstracts that mention this gene using gpt5-mini (DeepDive), then prompting an LLM to review the resulting summary for issues and a final pass to fix the noted issues.
References
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Hoffmann, M., Kleine‑Weber, H., Schroeder, S., et al. SARS‑CoV‑2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell (2020). ↩ ↩2 ↩3
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Zhou, P., Yang, X.‑L., Wang, X.‑G., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature (2020). ↩
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Wrapp, D., Wang, N., Corbett, K. S., et al. Cryo‑EM structure of the 2019‑nCoV spike in the prefusion conformation. Science (2020). ↩
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Lan, J., Ge, J., Yu, J., et al. Structure of the SARS‑CoV‑2 spike receptor‑binding domain bound to the ACE2 receptor. Nature (2020). ↩ ↩2
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Yan, R., Zhang, Y., Li, Y., et al. Structural basis for the recognition of SARS‑CoV‑2 by full‑length human ACE2. Science (2020). ↩
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Shang, J., Wan, Y., Luo, C., et al. Cell entry mechanisms of SARS‑CoV‑2. Proc Natl Acad Sci U S A (2020). ↩
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Hamming, I., Timens, W., Bulthuis, M. L. C., et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol (2004). ↩
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Gupta, A., Madhavan, M. V., Sehgal, K., et al. Extrapulmonary manifestations of COVID‑19. Nat Med (2020). ↩
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Kuba, K., Imai, Y., Rao, S., et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus‑induced lung injury. Nat Med (2005). ↩
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Wan, Y., Shang, J., Graham, R., et al. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade‑Long Structural Studies of SARS Coronavirus. J Virol (2020). ↩
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