COVID‐19, pulmonary mast cells, cytokine storms, and beneficial actions of luteolin

Abstract

Dear EditorThe new coronavirus (severe acute pulmonary syndrome [SARS]-CoV-2) originated in China, where it spread rapidly, 1 and has reached pandemic proportions because of its high rate of infectivity as well as high morbidity and mortality, associated with This coronavirus infects by first binding to the ectoenzyme angiotensinconverting enzyme 2 (ACE 2 ), 3,4 a serine protease acting as the receptor, while another serine protease is necessary for priming the viral "S" protein required for entering the cells. 5 Defense against the virus apparently does not involve inflammatory cytokines, 6 but pulmonary infection and its serious sequelae result from the release of multiple chemokines and cytokines that damage the lungs.A recent report correlated coronaviruses infection with activation of mast cells and subsequent cytokine storms in the lungs. 7 Mast cells are known to be triggered by viruses. 8 Mast cells are unique immune cells that are ubiquitous in the body, especially the lungs, 9 and are critical for allergic and pulmonary diseases, 10 including mastocytosis 11 by secreting histamine, leukotrienes, and proteases. Mast cells are also involved in the development of inflammation 12 via release of multiple pro-inflammatory cytokines and chemokines. 13,14 Mast cells contain the serine protease ACE 2 , which can convert angiotensin I into angiotensin II. 15 In addition to the bronchoconstrictive action of mast cell-derived leukotrienes, mast cells cause further bronchoconstriction via an active renin-angiotensin generating system in the lungs. 16 Moreover, mast cells express a number of serine proteases, 17 especially the mast cell-serine protease tryptase, 18 which are necessary for infection by SARS-CoV-2. A serine protease inhibitor, camostat mesylate, was recently shown to prevent entry of the virus into the lung cells of SARS-CoV-2-infected patients. 19 It would be important to not only inhibit entry of SARS-CoV-2 but also prevent SARS associated with COVID-19.The possible use of nonsteroidal anti-inflammatory agents has come into question for possibly aggravating pulmonary symptoms, 20 while broad-spectrum immune suppressors, such as corticosteroids, 21 would not be advisable given that an intact immune system is necessary to fight the infection and it may even lead to increased plasma viral load. 22 Inhibition of mast cell-associated inflammation could be accomplished with natural molecules, especially the polyphenolic flavonoids. 23 The flavone luteolin (not lutein, which is a carotenoid) has been shown to have broad antiviral properties. [24][25][26] Luteolin specifically binds to the surface spike protein of SARS-Cov-2 and inhibits entry of the virus into host cells. 27 Furthermore, luteolin inhibits serine proteases, 28 including the SARS-CoV 3CL protease 29 required for viral infectivity.Moreover, luteolin inhibits mast cells 30,31 and has anti-inflammatory properties. 32 A novel luteolin analogue, tetramethoxyluteolin, is even more potent 32 and can also inhibit secretion of the pro-inflammatory cy...

Molecular Alterations Prompted by SARS-CoV-2 Infection: Induction of Hyaluronan, Glycosaminoglycan and Mucopolysaccharide Metabolism

“…Mast cells secrete L-6, IL-1, IL-31, IL-33 and TNF, and chemokines CC5, CCL2, MCP-1 and CXCL8 which attract white blood cells to the inflammatory sites. Experiments with coronavirus in mice have shown that this pathogenic RNA microorganism can activate the cells of both innate and adaptive immune systems, including MCs (19,20).…”

Potential association of mast cells with coronavirus disease 2019

“…The pulmonary pathology associated with COVID-19 appears to result from release of multiple pro-inflammatory cytokines, especially IL-6, that can damage the lungs. 3 A key source of such cytokines and chemokines is the mast cells, which are ubiquitous in the body, especially the lungs, and are critical for allergic and pulmonary diseases. 3 In fact, activated mast cells were recently detected in the lungs of deceased patients with COVID-19 and were linked to pulmonary edema, inflammation and thromboses.…”

Do natural antioxidants play a role in Alzheimer's disease?

“…Some of these plant foods such as winter squash are also excellent sources of protease inhibitors that are bioavailable and can help prevent blood clotting, a death causing factor in COVID-19 (Otlewski and Krowarsch, 1996). When minimally processed, these foods can serve as good sources of protease inhibitors that can deliver these bioactives daily and may help individuals fight SARS-CoV-2 in-Food science research contribution to SARS CoV-2 and COVID-19 Losso fection (Otlewski and Krowarsch, 1996;Srikanth and Chen, 2016;Theoharides, 2020). The rate of SARS-CoV-2 infectivity and COVID-19-induced mortality appears to be low in countries where minimally processed foods rich in protease inhibitors are consumed regularly and in sizable quantities.…”