Melatonin potentials against viral infections including COVID-19: Current evidence and new findings

Juybari, Kobra Bahrampour; Pourhanifeh, Mohammad Hossein; Hosseinzadeh, Azam; Karim, Helmet T.; Mehrzadi, Saeed

doi:10.1016/j.virusres.2020.198108

Cited by 104 publications

(99 citation statements)

References 199 publications

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“…By contrast, exogenous estrogen application can increase OXT secretion, OTR mRNA expression in mouse brain [ 67 ], and intracardiac OTR signaling [ 68 ], which simulates the physiology of young women who are less susceptible than menopausal women to COVID-19. In addition, melatonin, a pineal hormone that has remarkable anti-inflammatory effects and can antagonize various viral infections including COVID-19 [ 69 ], can also regulate OXT release [ 70 ]. Thus, the susceptibility to COVID-19 is highly correlated with the activity of the OXT-secreting system.…”

Section: Oxt Functions Against Covid-19-associated CV Injuriesmentioning

confidence: 99%

Cardiovascular protective properties of oxytocin against COVID-19

Wang

2021

Life Sciences

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Section: Oxt Functions Against Covid-19-associated CV Injuriesmentioning

confidence: 99%

Cardiovascular protective properties of oxytocin against COVID-19

Wang

2021

Life Sciences

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“…There appears to be no standard approach to treating cytokine release syndromes that currently addresses all three, and the vast majority address none, focusing instead on antagonizing cytokine functions. However, melatonin (N-acetyl-5-methoxy tryptamine) has recently emerged as an effective therapy for severe COVID-19 [ 246 , 247 , 248 , 249 , 250 , 251 ]. While melatonin is often thought of being mainly a sleep regulator, it also has widespread effects on the innate immunity—in particular, antagonizing TLR2, TLR4, TLR9, NLRP3 and, possibly, NOD2 [ 59 , 252 , 253 , 254 , 255 ].…”

Section: Discussionmentioning

confidence: 99%

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

Root‐Bernstein

2021

IJMS

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Severe COVID-19 is characterized by a “cytokine storm”, the mechanism of which is not yet understood. I propose that cytokine storms result from synergistic interactions among Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLR) due to combined infections of SARS-CoV-2 with other microbes, mainly bacterial and fungal. This proposition is based on eight linked types of evidence and their logical connections. (1) Severe cases of COVID-19 differ from healthy controls and mild COVID-19 patients in exhibiting increased TLR4, TLR7, TLR9 and NLRP3 activity. (2) SARS-CoV-2 and related coronaviruses activate TLR3, TLR7, RIG1 and NLRP3. (3) SARS-CoV-2 cannot, therefore, account for the innate receptor activation pattern (IRAP) found in severe COVID-19 patients. (4) Severe COVID-19 also differs from its mild form in being characterized by bacterial and fungal infections. (5) Respiratory bacterial and fungal infections activate TLR2, TLR4, TLR9 and NLRP3. (6) A combination of SARS-CoV-2 with bacterial/fungal coinfections accounts for the IRAP found in severe COVID-19 and why it differs from mild cases. (7) Notably, TLR7 (viral) and TLR4 (bacterial/fungal) synergize, TLR9 and TLR4 (both bacterial/fungal) synergize and TLR2 and TLR4 (both bacterial/fungal) synergize with NLRP3 (viral and bacterial). (8) Thus, a SARS-CoV-2-bacterium/fungus coinfection produces synergistic innate activation, resulting in the hyperinflammation characteristic of a cytokine storm. Unique clinical, experimental and therapeutic predictions (such as why melatonin is effective in treating COVID-19) are discussed, and broader implications are outlined for understanding why other syndromes such as acute lung injury, acute respiratory distress syndrome and sepsis display varied cytokine storm symptoms.

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“…The deadly outbreak of Covid-19 imposes immense therapeutic challenges. Interestingly, based on positive outcomes in many viral infections, melatonin therapy for viral infections like Covid-19 seems promising [ 198 , 199 ]. Clinically, it has been shown that melatonin has a therapeutic potential even in cases exhibiting obesity or diabetes in coexistence with Covid-19 [ 200 ].…”

Section: Therapeutic Role Of Melatonin On Post Infection Complicatmentioning

confidence: 99%

Role of Melatonin on Virus-Induced Neuropathogenesis—A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection

et al. 2021

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Viral infections may cause neurological disorders by directly inducing oxidative stress and interrupting immune system function, both of which contribute to neuronal death. Several reports have described the neurological manifestations in Covid-19 patients where, in severe cases of the infection, brain inflammation and encephalitis are common. Recently, extensive research-based studies have revealed and acknowledged the clinical and preventive roles of melatonin in some viral diseases. Melatonin has been shown to have antiviral properties against several viral infections which are accompanied by neurological symptoms. The beneficial properties of melatonin relate to its properties as a potent antioxidant, anti-inflammatory, and immunoregulatory molecule and its neuroprotective effects. In this review, what is known about the therapeutic role of melatonin in virus-induced neuropathogenesis is summarized and discussed.

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Melatonin potentials against viral infections including COVID-19: Current evidence and new findings

Abstract: Highlights Viral infections are serious life-threatening and problematic human diseases. Melatonin can regulate human immune responses. Melatonin could be beneficial against different viral complications. In combination with other drugs, melatonin may play therapeutic role in COVID-19.

Cited by 104 publications

References 199 publications

Cardiovascular protective properties of oxytocin against COVID-19

Cardiovascular protective properties of oxytocin against COVID-19

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

Role of Melatonin on Virus-Induced Neuropathogenesis—A Concomitant Therapeutic Strategy to Understand SARS-CoV-2 Infection

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