ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?

Int J Mol Sci. 2021 Feb 8;22(4):1705. doi: 10.3390/ijms22041705.


Patients with coronavirus disease 2019 (COVID-19) have a wide variety of clinical outcomes ranging from asymptomatic to severe respiratory syndrome that can progress to life-threatening lung lesions. The identification of prognostic factors can help to improve the risk stratification of patients by promptly defining for each the most effective therapy to resolve the disease. The etiological agent causing COVID-19 is a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that enters cells via the ACE2 receptor. SARS-CoV-2 infection causes a reduction in ACE2 levels, leading to an imbalance in the renin-angiotensin system (RAS), and consequently, in blood pressure and systemic vascular resistance. ERAP1 and ERAP2 are two RAS regulators and key components of MHC class I antigen processing. Their polymorphisms have been associated with autoimmune and inflammatory conditions, hypertension, and cancer. Based on their involvement in the RAS, we believe that the dysfunctional status of ERAP1 and ERAP2 enzymes may exacerbate the effect of SARS-CoV-2 infection, aggravating the symptomatology and clinical outcome of the disease. In this review, we discuss this hypothesis.

Keywords: COVID-19; ERAP1; ERAP2; renin–angiotensin system; risk factor.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism*
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • Antigen Presentation / genetics
  • COVID-19 / metabolism*
  • COVID-19 / virology
  • Female
  • Humans
  • Hypertension / enzymology*
  • Hypertension / genetics
  • Male
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism*
  • Polymorphism, Single Nucleotide
  • Renin-Angiotensin System*
  • SARS-CoV-2 / metabolism*
  • Sex Factors
  • Virus Internalization


  • Minor Histocompatibility Antigens
  • Aminopeptidases
  • ERAP1 protein, human
  • ERAP2 protein, human
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2