Angiotensin-converting enzyme 2 (ACE2) (ACE2)

Angiotensin-converting enzyme 2 (ACE2) is a zinc-containing metallomonocarboxypeptidase and a vital component of the renin-angiotensin system (RAS), where it counterbalances the effects of ACE by converting angiotensin II into the cardioprotective peptide angiotensin (1-7) [UniProt: Q9BYF1]. It is expressed across various tissues, including the lungs, heart, and kidneys, playing a crucial role in regulating blood pressure and fluid balance [PubMed: 32125455]. ACE2 is also the primary functional receptor for the entry of SARS-CoV-2 into host cells, mediated by the viral spike protein's receptor-binding domain (RBD) [PubMed: 32142651]. The JN.1 variant, a descendant of the BA.2.86 lineage, possesses specific mutations such as L455S that enhance its immune evasion and maintain high binding affinity for ACE2 [PubMed: 38044431]. Therapeutic interventions, particularly the 2024-2025 updated COVID-19 vaccines, are designed to elicit antibodies that block this specific JN.1 spike-ACE2 interaction to prevent infection [FDA: 2024 Vaccine Update]. Additionally, recombinant ACE2 and small molecule inhibitors are being explored to treat both COVID-19 and cardiovascular conditions by modulating the RAS pathway [PubMed: 32661309].

Other names

ACE-related carboxypeptidaseACEHMetalloprotease MPROT15Angiotensin-converting enzyme homologPeptidyl-dipeptidase A 2

The primary mechanism of action for drugs targeting the ACE2-spike interaction involves competitive inhibition, where decoy receptors like recombinant human ACE2 (APN01) bind the viral spike protein to prevent its attachment to cellular ACE2 [PubMed: 32325032]. Small molecule inhibitors like MLN-4760 target the enzymatic site of ACE2 to modulate the renin-angiotensin system, while vaccines induce antibodies that sterically block the receptor-binding domain of the JN.1 spike protein from interacting with the ACE2 receptor surface [PubMed: 38044431, PubMed: 15030156].