Possible Prophylactic Approach for SARS-CoV-2 Infection by Combination of Melatonin, Vitamin C and Zinc in Animals

Abstract

SARS-CoV-2, an epidemic, causes severe stress in both human and animals and may induce oxidative stress (OS) and increases susceptibility to infection. Domestic animals are found infected by their COVID-2 suffering owners. Chronic immobilization stress (CIS), a model of psychological and physical stress of confinement, can trigger depression and anxiety in animals. We evaluated the ameliorative effect of the proposed SARS-CoV-2 prophylactic drugs melatonin, vitamin C, and zinc on CIS-induced OS, inflammation, and DNA damage in rats. Forty male Swiss albino rats (200–250 g, 7–9 weeks old) were divided into five groups as controls, CIS, treated with melatonin (20 mg/kg), and vitamin C plus zinc [VitC+Zn (250 + 2.5 mg/kg)] alone or in combination (melatonin+VitC+zinc) subjected to CIS for 3 weeks. CIS was induced by immobilizing the whole body of the rats in wire mesh cages of their size with free movement of head. Exposure to CIS significantly compromised the circulatory activities of superoxide dismutase, catalase, and glutathione with enhanced malondialdehyde, inflammatory markers (IL-6, IL10, and TNFα), and lymphocyte DNA damage in comparison to controls. Treatment with melatonin and VitC+Zn alone or in combination significantly restored the altered biochemical parameters and DNA damage of stressed rats to their respective control values. However, the cumulative action of melatonin with VitC+Zn was more effective in alleviating the CIS-induced OS, inflammation, and DNA damage. The present study indicates that the antioxidant combination can be an effective preventive measure to combat severe psychological and confinement stress-induced biochemical changes in animals due to abnormal conditions such as SARS-CoV-2.

Potential and Possible Therapeutic Effects of Melatonin on SARS-CoV-2 Infection

“…It has anxiolytic, antidepressant, and sleeping effects, as well as the ability to reduce the consequences of stress [ 82 , 83 ]. The last is confirmed by an experimental study, where the combination of melatonin, vitamin C, and zinc was an effective preventive measure against severe psychological and chronic stress-induced biochemical manifestations of oxidative stress in rats due to abnormal conditions (e.g., SARS-CoV-2) [ 84 ]. According to a systematic review of 27 randomized controlled trials (involving 2319 participants), melatonin (doses varied from 3 to 10 mg per day) is more effective than a placebo in reducing anxiety.…”

Melatonin and multiple sclerosis: antioxidant, anti-inflammatory and immunomodulator mechanism of action

“…This inhibition gradually weakened with time, since the degree of inhibition is negatively related with the dosage of melatonin. Melatonin may regulate the activation of T/B cells, playing a critical role in the regulation of immune balance Kim et al ( 2020 ) TLR4-deficient BALB/c mice Male (Not specified) 8–9 weeks Inflammatory bowel disease 10 mg/kg/day (i.p) Melatonin significantly increases goblet cells and Reg3β by suppressing Gram-negative bacteria through TLR4 signalling Fatima et al ( 2020 ) Swiss albino rats Male (40) 7–9 weeks Chronic Immobilization Stress 20 mg/kg Treatment with melatonin and VitC + Zn alone or in combination significantly restored the altered biochemical parameters and DNA damage of stressed rats to their respective control values. However, the cumulative action of melatonin with VitC + Zn was more effective in alleviating the CIS-induced OS, inflammation, and DNA damage Fernandez-Ortiz et al ( 2020 ) C57BL/6 J Not specified (35) 3 weeks Aging 10 mg/kg/day (orally) Melatonin treatment recovered mitochondrial dynamics altered by aging.…”

“…Another of the effects triggered by COVID-19 is the activation of the inflammasome NLRP3, which sets off the so-called “cytokine storm” (Fatima et al 2020 ), that causes lung inflammation, lesions, and the acute breathing difficulty syndrome (Wu et al 2019 ; Fatima et al 2020 ). Soares et al 2019 confirmed that these mechanisms entail a serious risk of developing MS and a progression towards more serious forms of the disease (Soares et al 2019 ).…”

“…Soares et al 2019 confirmed that these mechanisms entail a serious risk of developing MS and a progression towards more serious forms of the disease (Soares et al 2019 ). Melatonin can inhibit the inflammasomes activated by COVID-19 (Wu et al 2019 ; Fatima et al 2020 ), so that it would prevent the secretion of the proinflammatory cytokines IL-1β and IL-18 (Lahooti et al 2021 ) and reduce the lung condition caused by the virus.…”

Melatonin increased hypoxia‐inducible factor (HIF) by inhibiting prolyl hydroxylase: A hypothesis for treating anaemia, ischaemia, and covid‐19

“…Indeed, PH inhibitors stabilised the DNA of lymphocytes and ultimately increased the immune system's resistance. 16 Two randomised, double‐blind clinical trials showed that daily use of melatonin (3 mg/day) could significantly reduce cough rate, dyspnoea, fatigue, C‐reactive protein levels, pulmonary involvement, time of hospitalisation, time of return to baseline health, 9 and improve blood oxygen saturation. 10 Also, a meta‐analysis of three randomised controlled trials confirmed that MLT consumption increases clinical recovery rate, decreases risk of intensive care unit admission, and mortality rate in covid‐19 patients.…”