Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection

Abstract

Growing interest in hypertension—one of the main factors characterizing the cardiometabolic syndrome (CMS)—and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. Several classes of synthetic drugs are available for hypertension, rarely associated with severe or mild adverse effects. New natural compounds, such as peptides, might be useful to treat some hypertensive patients. The main feature of ACE inhibitory peptides is the location of the hydrophobic residue, usually Proline, at the C-terminus. Some already known bioactive peptides derived from marine resources have potential ACE inhibitory activity and can be considered therapeutic agents to treat hypertension. Peptides isolated from marine vertebrates, invertebrates, seaweeds, or sea microorganisms displayed important biological activities to treat hypertensive patients. Here, we reviewed the anti-hypertensive activities of bioactive molecules isolated/extracted from marine organisms and discussed the associated molecular mechanisms involved. We also examined ACE2 modulation in sight of SARS2-Cov infection prevention.

Functional and Bioactive Properties of Peptides Derived from Marine Side Streams

“…Angiotensin-converting enzyme (ACE) catalyzes specific reactions involved in blood pressure regulation, which makes this enzyme responsible for hypertension and a key target in the therapy of such a risk factor of cardiovascular disease. Antihypertensive peptides obtained from seafood have been extensively reviewed elsewhere [ 63 ], demonstrating that the recovery of these bioactive compounds is an efficient way of using seafood by-products. For instance, some studies have shown that peptides obtained through collagen hydrolysis from skate skin and sea cucumber can inhibit the activity of angiotensin-converting enzyme (ACE) [ 12 , 13 , 14 ], being a natural and potentially healthier alternative to synthetic ACE inhibitors available on the market.…”

“…On the other hand, if tyrosine is replaced by phenylalanine at the C-terminus, the systolic blood pressure will decrease rapidly but only for a short time [ 67 ]. Interestingly, next to the role of marine peptides in hypertension, recent studies have also reported that they could represent a promising approach in the intervention and prevention of Severe Acute Respiratory Syndrome (SARS) virus infection, through their ACE-II inhibitory properties [ 63 ].…”

Marine Organisms as a Rich Source of Biologically Active Peptides

“…SARS-CoV-2 enters cells via interactions between the Angiotensin-converting enzyme 2 (ACE2) and the Spike viral protein. Marine peptides with antiviral and anti-ACE2 activity can be an alternative tool in solving this problem (Festa et al, 2020). From this echinoderm, four peptides were also isolated from the hydrolysis of collagen.…”

A comprehensive review of COVID-19 biology, diagnostics, therapeutics, and disease impacting the central nervous system

“…Vitamin D and calcitriol (which have known anti-inflammatory effects) are studied for their preemptive effects to help regulate angiotensin-renin mechanisms, which increase lipopolysaccharide permeability into lungs and reduce severe lung damage (Sarwar et al 2020 ; Xu et al 2017 ). Typical ACE2 inhibitors and receptor antagonists Captopril and enalapril, and iosartan and valsartan, respectively, are under study along with new inhibitory methods including single-chain variable fragments, VHH domains, nanobodies, fusion of human recombinant soluble ACE2 (hrsACE2) to an immune-adhesion molecule, and even the use of inhibitory peptides isolated from marine organisms (Festa et al 2020 ; Zhou et al 2020a , b , c ).…”