Generic placeholder image

Current Protein & Peptide Science


ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Mini-Review Article

COVID-19 and L-arginine Supplementations: Yet to Find the Missed Key

Author(s): Hayder M. Al-Kuraishy, Ali I. Al-Gareeb, Athanasios Alexiou* and Gaber El-Saber Batiha*

Volume 23, Issue 3, 2022

Published on: 31 May, 2022

Page: [166 - 169] Pages: 4

DOI: 10.2174/1389203723666220512104039

Price: $65


Current coronavirus disease (COVID-19) is regarded as a primary respiratory and vascular disease leading to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and endothelial dysfunction (ED) in severe cases. The causative virus of COVID-19 is SARS-CoV-2, which binds angiotensin-converting enzyme 2 (ACE2) for its entry. It has been shown that ED is linked to various COVID-19 complications since endothelial cells are regarded as the chief barrier against SARS-CoV- 2 invasion. SARS-CoV-2-indued ED leads to endotheliitis and thrombosis due to endothelial nitric oxide (NO) inhibition with subsequent vasoconstriction and tissue hypoxia. Loss of vasodilator NO and anti-thrombin factor from endothelial SARS-CoV-2 infection contribute to the progression of vascular dysfunction and coagulopathy. Therefore, NO restoration improves pulmonary function and hinders viral replication during respiratory viral infections, including COVID-19. L-arginine is a semiessential amino acid that has antiviral and immunomodulatory effects as well as improves the biosynthesis of NO in endothelial cells. L-arginine may reduce the risk of ALI through inhibition of generation of peroxynitrite and suppression of the release of proinflammatory cytokines from alveolar macrophages. Of interest, restoration of NO by L-arginine may attenuate SARS-CoV-2 infection through different mechanisms, including reduction binding of SARS-CoV-2 to ACE2, inhibition of transmembrane protease serine-type 2 (TMPRSS2), critical for the activation of SARS-CoV-2 spike protein and cellular entry, inhibition proliferation and replication of SARS-CoV-2, and prevention of SARS-CoV-2-induced coagulopathy. In conclusion, through antiviral and immunomodulatory effects, L-arginine and released NO have mutual and interrelated actions against SARS-CoV-2 infection.

Keywords: SARS-CoV-2, COVID-19, L-arginine, antiviral effects, immunomodulatory effects, endothelial nitric oxide.

Graphical Abstract
Lugnier, C.; Al-Kuraishy, H.M.; Rousseau, E. PDE4 inhibition as a therapeutic strategy for improvement of pulmonary dysfunctions in COVID-19 and cigarette smoking. Biochem. Pharmacol., 2021, 185, 114431-114438.
[] [PMID: 33515531]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Faidah, H.; Al-Maiahy, T.J.; Cruz-Martins, N.; Batiha, G.E. The looming effects of estrogen in COVID-19: A Rocky Rollout. Front. Nutr., 2021, 8, 649128.
[] [PMID: 33816542]
Al-Kuraishy, H.M.; Al-Gareeb, A.I.; Alblihed, M.; Cruz-Martins, N.; Batiha, G.E. COVID-19 and risk of acute ischemic stroke and acute lung injury in patients with type ii diabetes mellitus: the anti-inflammatory role of metformin. Front. Med. (Lausanne), 2021, 8, 644295.
[] [PMID: 33718411]
Bonaventura, A.; Vecchié, A.; Dagna, L.; Martinod, K.; Dixon, D.L.; Van Tassell, B.W.; Dentali, F.; Montecucco, F.; Massberg, S.; Levi, M.; Abbate, A. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat. Rev. Immunol., 2021, 21(5), 319-329.
[] [PMID: 33824483]
Sims, J.T.; Krishnan, V.; Chang, C.Y.; Engle, S.M.; Casalini, G.; Rodgers, G.H.; Bivi, N.; Nickoloff, B.J.; Konrad, R.J.; de Bono, S.; Higgs, R.E.; Benschop, R.J.; Ottaviani, S.; Cardoso, A.; Nirula, A.; Corbellino, M.; Stebbing, J. Characterization of the cytokine storm reflects hy-perinflammatory endothelial dysfunction in COVID-19. J. Allergy Clin. Immunol., 2021, 147(1), 107-111.
[] [PMID: 32920092]
Lotz, C.; Muellenbach, R.M.; Meybohm, P.; Mutlak, H.; Lepper, P.M.; Rolfes, C.B.; Peivandi, A.; Stumpner, J.; Kredel, M.; Kranke, P.; Torje, I.; Reyher, C. Effects of inhaled nitric oxide in COVID-19-induced ARDS - Is it worthwhile? Acta Anaesthesiol. Scand., 2021, 65(5), 629-632.
[] [PMID: 33296498]
Yang, Y.; Huang, Z.; Li, L.L. Advanced nitric oxide donors: chemical structure of NO drugs, NO nanomedicines and biomedical applica-tions. Nanoscale, 2021, 13(2), 444-459.
[] [PMID: 33403376]
Wolf, S.T.; Jablonski, N.G.; Ferguson, S.B.; Alexander, L.M.; Kenney, W.L. Four weeks of vitamin D supplementation improves nitric oxide-mediated microvascular function in college-aged African Americans. Am. J. Physiol. Heart Circ. Physiol., 2020, 319(4), H906-H914.
[] [PMID: 32857616]
Liddle, L.; Burleigh, M.C.; Monaghan, C.; Muggeridge, D.J.; Sculthorpe, N.; Pedlar, C.R.; Butcher, J.; Henriquez, F.L.; Easton, C. Variabil-ity in nitrate-reducing oral bacteria and nitric oxide metabolites in biological fluids following dietary nitrate administration: An assessment of the critical difference. Nitric Oxide, 2019, 83, 1-10.
[] [PMID: 30528912]
Adusumilli, N.C.; Zhang, D.; Friedman, J.M.; Friedman, A.J. Harnessing nitric oxide for preventing, limiting and treating the severe pul-monary consequences of COVID-19. Nitric Oxide, 2020, 103, 4-8.
[] [PMID: 32681986]
Liu, H.; Xiong, X.; Zhu, T.; Zhu, Y.; Peng, Y.; Zhu, X.; Wang, J.; Chen, H.; Chen, Y.; Guo, A. Differential nitric oxide induced by Myco-bacterium bovis and BCG leading to dendritic cells apoptosis in a caspase dependent manner. Microb. Pathog., 2020, 149, 104303.
[] [PMID: 32504845]
Guan, S.P.; Seet, R.C.S.; Kennedy, B.K. Does eNOS derived nitric oxide protect the young from severe COVID-19 complications? Ageing Res. Rev., 2020, 64, 101201.
[] [PMID: 33157320]
Szefel, J.; Danielak, A.; Kruszewski, W.J. Metabolic pathways of L-arginine and therapeutic consequences in tumors. Adv. Med. Sci., 2019, 64(1), 104-110.
[] [PMID: 30605863]
Maas, R.; Xanthakis, V.; Göen, T.; Müller, J.; Schwedhelm, E.; Böger, R.H.; Vasan, R.S. Plasma nitrate and incidence of cardiovascular disease and all-cause mortality in the community: The Framingham Offspring Study. J. Am. Heart Assoc., 2017, 6(11), e006224.
[] [PMID: 29151027]
Huang, S.; Qu, H.; Huang, D.; Geng, Z. Effects of L-arginine on growth performance, immune function and genes expression levels of tumor necrosis factor-α and interferon-γ in liver and kidney of cold-stressed piglets. Chinese J. Animal Nutr., 2019, 31(1), 131-139.
Gruber, C. Impaired interferon signature in severe COVID-19. Nat. Rev. Immunol., 2020, 20(6), 353.
[] [PMID: 32355328]
Zhang, H.; Zhao, F.; Peng, A.; Dong, L.; Wang, M.; Yu, L.; Loor, J.J.; Wang, H. Effects of dietary l-arginine and N-carbamylglutamate supplementation on intestinal integrity, immune function, and oxidative status in intrauterine-growth-retarded suckling lambs. J. Agric. Food Chem., 2018, 66(16), 4145-4154.
[] [PMID: 29595256]
Murakami, K.; Enkhbaatar, P.; Yu, Y.M.; Traber, L.D.; Cox, R.A.; Hawkins, H.K.; Tompkins, R.G.; Herndon, D.; Traber, D.L. L-arginine attenuates acute lung injury after smoke inhalation and burn injury in sheep. Shock, 2007, 28(4), 477-483.
[] [PMID: 17558346]
Lecleire, S.; Coeffier, M.; Leblond, J.; Hubert, A.; Lemoulan, S.; Petit, A.; Ducrotte, P.; Dechelotte, P.; Marion, R. Modulation of nitric oxide and cytokines production by L-arginine in human gut mucosa. Clin. Nutr., 2005, 24(3), 353-359.
[] [PMID: 15896421]
Mir, J.M.; Maurya, R.C. Nitric oxide as a therapeutic option for COVID-19 treatment: a concise perspective. New J. Chem., 2021, 45(4), 1774-1784.
Green, S.J. COVID-19 accelerates endothelial dysfunction and nitric oxide deficiency. Microbes Infect., 2020, 22(4-5), 149-150.
[] [PMID: 32425647]
Kroll, J.L.; Werchan, C.A.; Rosenfield, D.; Ritz, T. Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals. PLoS One, 2018, 13(1), e0191030.
[] [PMID: 29370244]
Behnia, M.; Wheatley, C.M.; Avolio, A.; Johnson, B.D. Influence of dietary nitrate supplementation on lung function and exercise gas exchange in COPD patients. Nitric Oxide, 2018, 76, 53-61.
[] [PMID: 29549005]
Kache, S.; Chisti, M.J.; Gumbo, F.; Mupere, E.; Zhi, X.; Nallasamy, K.; Nakagawa, S.; Lee, J.H.; Di Nardo, M.; de la Oliva, P.; Katyal, C.; Anand, K.J.S.; de Souza, D.C.; Lanziotti, V.S.; Carcillo, J. COVID-19 PICU guidelines: for high- and limited-resource settings. Pediatr. Res., 2020, 88(5), 705-716.
[] [PMID: 32634818]
Alvarez, R.A.; Berra, L.; Gladwin, M.T. Home nitric oxide therapy for COVID-19. Am. J. Respir. Crit. Care Med., 2020, 202(1), 16-20.
[] [PMID: 32437250]
Úbeda, C.M.; Parreño, J.D.T.; Iranzo, A.P. Non-invasive inhaled nitric oxide in term and preterm newborns: A therapeutic option in se-lected patients. An. Pediatr. (Barc.), 2022, 96(2), 161-164. [English Edition]
[] [PMID: 35131220]
Fiorentino, G.; Coppola, A.; Izzo, R.; Annunziata, A.; Bernardo, M.; Lombardi, A.; Trimarco, V.; Santulli, G.; Trimarco, B. Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis. EClinicalMedicine, 2021, 40, 101125.
[] [PMID: 34522871]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy