In the current global pandemic, research on the treatment of COVID-19 is ongoing. The therapeutic potential of Vasoactive Peptides has been studied by a team of researchers in Tehran, Iran, and published in Archives of Medical Research, “Vasoactive Peptides: Pathogenesis of COVID-19 Pathogenesis and Potential Use as Biomarkers and Therapeutic Targets. The study concluded that assessment of vasoactive peptides should be considered as a routine part of COVID-19 patient monitoring and that they can be used as potential therapeutic targets for disease management.

Current clinical features of COVID-19 range from asymptomatic status to severe acute respiratory failure and multiple organ dysfunction. Common clinical symptoms include fever, dry cough, loss of smell, sore throat, shortness of breath, fatigue, headache, and myalgia. In addition, several patients with COVID-19 reported multiple organ dysfunction, such as cardiovascular complications, renal failure, gastrointestinal symptoms, hematological symptoms, and neurological manifestations.

Given the urgent need to explore specific therapeutic targets and biomarkers for emerging COVID-19, a research team in Tehran, Iran, discussed the potential of vasoactive peptides, Angiotensin II(Ang II), vasoactive intestinal peptide (VIP), endothelin-1 (ET-1), calcitonin gene-related peptide (CGRP), natriuretic peptide, substance P (SP), and bradykinin (BK) are included as therapeutic targets and/or prognostic indicators for the COVID-19 pandemic.

Vasoactive peptides in COVID-19

Angiotensin II (Ang II), an octapeptide, is a major effector of the renin-angiotensin system (RAS). It plays a crucial role in homeostasis, blood pressure control, and heart and blood vessel function.

Vasoactive intestinal peptide (VIP) is a kind of 28 amino acid peptide, has extensive physiological functions, including effective bronchiectasis and vasodilation function, enhance the circulation of the blood of the heart and lungs, effective anti-inflammatory effects, regulating the airway epithelial secretion, on vascular smooth muscle cell proliferation, regulate the inhibition of cell growth and survival

Endotherin (ET) contains four peptides of 21 amino acids with different structures, including ET-1, ET-2, ET-3, and ET-4. Mature ET-1 is thought to be an endothelium-derived contraction factor, produced by ET-1, a precursor of the endothelin invertase family and other enzymes. ET-1 exerts its function through two G protein-coupled receptors, homotype ETA and ETB, which have the same affinity. It is widely believed that ET-1 is one of the most effective vasopressor drugs known in the whole human cardiovascular system, which can exert a strong vasopressor effect on a variety of blood vessels.

Calcitonin gene-related peptide (CGRP) is an effective vasodilator, angiogenesis and immunomodulatory peptide, mainly located in the peripheral and central sensory nervous system. CGRP is a therapeutic target for migraine because of its supposed function as a mediator of trigeminal vascular pain transmission and as a vasodilator of neurogenic inflammation.

As a group of circulating peptide hormones, natriuretic peptides are key regulators of cardiac and renal homeostasis and a variety of metabolic processes. Up to now, there have been eight kinds of natriuretic peptides, including ANP, BNP, C-type natriuretic peptide (CNP), dendrobium natriuretic peptide (DNP), urodilatin, uroguanosin, osteocrine and myosin. These peptides are primarily released by the heart and are known as cardiac hormones. Their plasma levels have long been used as diagnostic and prognostic biomarkers in patients with cardiovascular disease.

Substant P (SP) is a neuropeptide composed of 11 amino acid residues, belonging to the tachykinin neuropeptide family. The biological effects of SP are mediated by its receptor neurokinin type 1 receptor (NK-1R), which consists of seven transmembrane domains, GPCR. Although SP is widely distributed in the nervous system as a neurotransmitter/neuromodulator in pain perception, SP is involved in the regulation of inflammation and immune response, hematopoiesis, vasodilation, chemotaxis, cell survival and proliferation through interaction with NK1R, and plays a role in respiration, gastrointestinal tract and other mechanisms.

The kallikinase – kallikin system (KKS) is involved in blood pressure regulation, inflammatory response, pain, blood clotting, and cell proliferation. Kinin is induced by the release of vasodilators including peptides prostaglatin E2 and prostacyclin, nitric oxide (NO), and endothelial-derived hyperpolarizing factor (EDHF) to increase vascular permeability and arterial dilation in vascular beds such as skeletal muscle, liver, kidney, heart, and intestine. Kinin action is mediated by two distinct G-protein-coupled receptors called bradykinin receptors B1 and B2.

The COVID-19 pandemic is an emerging and rapidly evolving epidemic with an unprecedented timetable to develop effective drugs to control the disease. Currently, extensive experimental and clinical studies are underway to investigate the therapeutic and biomarker potential of vasoactive peptides in the treatment of COVID-19 complications, particularly ARDS and cardiovascular comorbidities, which remain to be proven. Most changes in these peptides are associated with the presence of the disease and a more severe prognosis. Thus, the use of vasoactive peptides as a marker or therapeutic target may help to understand the pathogenesis of COVID-19 and modulate the immune response after infection to limit coronavirus-associated complications and mortality.