Renin-angiotensin system in human coronavirus pathogenesis

Abstract

Although initially considered relatively harmless pathogens, human coronaviruses (HCoVs) are nowadays known to be associated with more severe clinical complications. Still, their precise pathogenic potential is largely unknown, particularly regarding the most recently identified species HCoV-NL63 and HCoV-HKU1. HCoVs need host cell proteins to successively establish infections. Proteases of the renin-angiotensin system serve as receptors needed for entry into target cells; this article describes the current knowledge on the involvement of this system in HCoV pathogenesis.

Keywords: SARS-CoV; aminopeptidase N; angiotensin-converting enzyme 2; human coronavirus 229E; human coronavirus NL63; renin–angiotensin system; virus–host interactions.

Figure 1.. Overview of the most important renin–angiotensin components and mediated physiological effects.

Linear enzymatic cascade depicted in the middle represents the classical renin–angiotensin system (RAS) and yields the effector peptide Ang II that can interact with AT₁R or AT₂R. The more complex RAS is capable of producing additional biologically active angiotensin fragments with independent actions, including Ang III, Ang (1–7) and Ang IV. Depicted colored pathways: (red) main ACE–Ang II–AT₁ receptor axis, (blue) putative counter-regulatory arm of the RAS, involving ACE2–Ang (1–7)–MAS R. This dual function system is primarily driven by the ACE/ACE2 balance. ACE: Angiotensin-converting enzyme; ADH: Antidiuretic hormone or vasopressin; Ang: Angiotensin; APA: Aminopeptidase A; APB: Aminopeptidase B; APN: Aminopeptidase N; AT₁R: Angiotensin II receptor type 1; AT₂R: Angiotensin II receptor type 2; AT₄R: Angiotensin receptor type 4; MASR: MAS receptor; NEP: Neprilysin or neutral endopeptidase; NF-κB: Nuclear factor-κB; NO: Nitric oxide; PCP: Prolyl carboxypeptidase; PEP: Prolyl carboxypeptidase.