Title:Targeting and Modulation of the Natriuretic Peptide System in Covid-19:
A Single or Double-Edged Effect?
Volume: 23
Issue: 5
Author(s): Hayder M. Al-kuraishy, Ali I. Al-Gareeb, Athanasios Alexiou*Gaber El-Saber Batiha*
Affiliation:
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, Australia
- AFNP Med Austria, Wien, Austria
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine,
Damanhour University, Damanhour 22511, AlBeheira, Egypt
Keywords:
Covid-19, sacubitril, neprilysin, natriuretic peptide system, anti-inflammatory effects, acute lung injury, respiratory distress syndrome.
Abstract:
Natriuretic peptide system (NPS) is a group of peptide hormones or paracrine factors, including
atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and natriuretic peptide precursor
C (NPC), that are structurally related. The physiological effects of NPS include natriuresis, increased
glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic
inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological
effects, as it is produced locally from immune cells; it regulates innate and adaptive immune responses.
Metabolism and degradation of ANP are achieved by neutral endopeptidase (NEP), also known as
neprilysin. Coronavirus disease 2019 (Covid-19) pandemic may lead to acute lung injury (ALI) and/or
respiratory distress syndrome (ARDS). The underlying causes of inflammatory and immunological
disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent
release of pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels
regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs,
which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin
inhibitors like sacubitril increase endogenous NPs and may reduce the risk of ALI in Covid-19
due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases
gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by
neprilysin.
In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced
ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing
vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of
neprilysin inhibitors in managing Covid-19.