Melatonin: A potential therapeutic agent against COVID-19

2021 ◽  
Vol 4 (1) ◽  
pp. 30-69
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Youngsok Choi ◽  
Russel J Reiter ◽  
Jin-Hoi Kim

Coronaviruses (CoVs) are RNA viruses that cause infections of the respiratory, gastrointestinal, and central nervous systems, among others. The pathological symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) include excessive inflammation, elevated oxidative stress, and an exaggerated immune response, ultimately leading to a cytokine storm and  subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often, death. Melatonin is a multifunctional and highly significant biomolecule that has anti-inflammatory, anti-oxidative, anti-apoptotic, and neuroprotective actions with no serious undesired side effects, even when administered in high doses. In this review, we present a brief account of the origin of coronaviruses, their characteristic features, infections, transmission, and the causes of coronavirus disease 2019 (COVID-19). We discuss their structure, genome organization, and mechanisms of cellular entry, as well as the pathogenicity of severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. Furthermore, we provide an account of the typical characteristic features of melatonin, such as its antioxidant, anti-inflammatory, immunomodulatory, and ameliorative effects on various virus-induced infections. Additionally, we identify the rationale for using melatonin as both a prospective adjuvant with vaccine therapy, and as an antiviral immune stimulator. Finally, we provide a perspective on the use of melatonin as a treatment against COVID-19.   

2020 ◽  
Vol 73 (1) ◽  
Author(s):  
Olena Koloskova ◽  
Tetiana Bilous ◽  
Galyna Bilyk ◽  
Kristina Buryniuk-Glovyak ◽  
Olena Korotun ◽  
...  

The aim: To study the clinical and spirographic features persistence of the bronchial asthma in schoolchildren against the background of the alternative daily doses of inhaled corticosteroids to increase the effectiveness of anti-inflammatory therapy for this disease. Materials and methods: A complete comprehensive clinical-paraclinical examination of 65 schoolchildren with persistent asthma was conducted. According to the average daily dose of inhaled corticosteroids (ICS) the patients were divided into two clinical groups. The first (I) group consisted of 46 children who received ICS in the regimen of low-to-medium equipotent doses (253.95±9.98 μg per day), and the second (II) comparison group was formed of 19 patients who controlled the pBA using high doses of ICS (494.74±5.56 μg per day). Results: The patients of the І clinical group compared to patients of the ІІ group have a higher risk of the mild bronchial obstructive syndrome during asthma attacks. In assessing the level of control of persistent bronchial asthma using the CIA-scale, it was found that in II group cases of the controlled course of the disease were observed almost two times less than in children of the I group of comparison. In conducting spirography in children of comparison groups, it was shown that the ratio of indices of bronchospasm (FEV1/ FVC) was worse in patients receiving high doses of ICS. Conclusions: So, сharacteristic clinical feature of asthma controlled by high doses of ICS is more severe nature of bronchial obstructive syndrome during the period of exacerbation (OR=1.9-3.0). In the management of persistent bronchial asthma, the Gensler index which has high specificity (94.4%) and accuracy (92.2%) should be used for disease control verification.


Author(s):  
Mona Aslani ◽  
Arman Ahmadzadeh ◽  
Zahra Aghazadeh ◽  
Majid Zaki-Dizaji ◽  
Laleh Sharifi ◽  
...  

Background: : Based on the encouraging results of phase III clinical trial of β-D-mannuronic acid (M2000) (as a new anti-inflammatory drug) in patients with RA, in this study, we aimed to evaluate the effects of this drug on the expression of chemokines and their receptors in PBMCs of RA patients. Methods:: PBMCs of RA patients and healthy controls were separated and the patients' cells were treated with low, moderate and high doses (5, 25 and 50 μg/mL) of M2000 and optimum dose (1 μg/mL) of diclofenac, as a control in RPMI-1640 medium. Real-time PCR was used for evaluating the mRNA expression of CXCR3, CXCR4, CCR2, CCR5 and CCL2/MCP-1. Cell surface expression of CCR2 was investigated using flow cytometry. Results:: CCR5 mRNA expression reduced significantly, after treatment of the patients' cells with all three doses of M2000 and optimum dose of diclofenac. CXCR3 mRNA expression down-regulated significantly followed by treatment of these cells with moderate and high doses of M2000 and optimum dose of diclofenac. CXCR4 mRNA expression declined significantly after treatment of these cells with moderate and high doses of M2000. CCL2 mRNA expression significantly reduced only followed by treatment of these cells with high dose of M2000, whereas, mRNA and cell surface expressions of CCR2 diminished significantly followed by treatment of these cells with high dose of M2000 and optimum dose of diclofenac. Conclusion:: According to our results, M2000 through the down-regulation of chemokines and their receptors may restrict the infiltration of immune cells into the synovium.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 774
Author(s):  
Chengfeng Gao ◽  
Chunxia Wen ◽  
Zhifeng Li ◽  
Shuhan Lin ◽  
Shu Gao ◽  
...  

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.


Author(s):  
Emanuele Pontali ◽  
Stefano Volpi ◽  
Alessio Signori ◽  
Giancarlo Antonucci ◽  
Marco Castellaneta ◽  
...  
Keyword(s):  

2014 ◽  
Vol 389 (1-2) ◽  
pp. 84-91 ◽  
Author(s):  
Quan-Guang Zhang ◽  
Ruimin Wang ◽  
Hui Tang ◽  
Yan Dong ◽  
Alice Chan ◽  
...  

2017 ◽  
Vol 8 (6) ◽  
pp. 173-182 ◽  
Author(s):  
Andrea Fanelli ◽  
Daniela Ghisi ◽  
Pierangelo Lora Aprile ◽  
Francesco Lapi

Observational studies and meta-analyses have shown that the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), especially when prescribed at high doses for long periods of time, can potentially increase the risk of cardiovascular diseases. The increased thrombotic risk related to the use of NSAIDs is mainly due to their cyclooxygenase 2 selectivity. The dosage use, the formulation selected and the duration of the therapy are other factors that can significantly impact on the cardiovascular risk. In order to minimize the risk, prescription of the right drug based on the patient’s features and the different safety profiles of several NSAIDs that are available on the market is key for their appropriate administration. Despite the baseline cardiovascular and gastrointestinal risk of each patient, monitoring of patients is suggested for increases in blood pressure, development of edema, deterioration of renal function, or gastrointestinal bleeding during long-term treatment with NSAIDs.


Author(s):  
Azzeddine Kermad ◽  
Jacques Speltz ◽  
Guy Danziger ◽  
Thilo Mertke ◽  
Robert Bals ◽  
...  

Abstract Purpose In this retrospective study, we compared inhaled sedation with isoflurane to intravenous propofol in invasively ventilated COVID-19 patients with ARDS (Acute Respiratory Distress Syndrome). Methods Charts of all 20 patients with COVID-19 ARDS admitted to the ICU of a German University Hospital during the first wave of the pandemic between 22/03/2020 and 21/04/2020 were reviewed. Among screened 333 days, isoflurane was used in 97 days, while in 187 days, propofol was used for 12 h or more. The effect and dose of these two sedatives were compared. Mixed sedation days were excluded. Results Patients’ age (median [interquartile range]) was 64 (60–68) years. They were invasively ventilated for 36 [21–50] days. End-tidal isoflurane concentrations were high (0.96 ± 0.41 Vol %); multiple linear regression yielded the ratio (isoflurane infusion rate)/(minute ventilation) as the single best predictor. Infusion rates were decreased under ECMO (3.5 ± 1.4 versus 7.1 ± 3.2 ml∙h−1; p < 0.001). In five patients, the maximum recommended dose of propofol of 4 mg∙hour−1∙kg−1ABW was exceeded on several days. On isoflurane compared to propofol days, neuro-muscular blocking agents (NMBAs) were used less frequently (11% versus 21%; p < 0.05), as were co-sedatives (7% versus 31%, p < 0.001); daily opioid doses were lower (720 [720–960] versus 1080 [720–1620] mg morphine equivalents, p < 0.001); and RASS scores indicated deeper levels of sedation (− 4.0 [− 4.0 to − 3.0] versus − 3.0 [− 3.6 to − 2.5]; p < 0.01). Conclusion Isoflurane provided sufficient sedation with less NMBAs, less polypharmacy and lower opioid doses compared to propofol. High doses of both drugs were needed in severely ill COVID-19 patients.


2021 ◽  
pp. 19-23
Author(s):  
Donizete Tavares Da Silva ◽  
Priscila De Sousa Barros Lima ◽  
Renato Sampaio Mello Neto ◽  
Gustavo Magalhães Valente ◽  
Débora Dias Cabral ◽  
...  

In March 2020, the World Health Organization (1) declared COVID-19 as a pandemic and a threat to global public health (2). The virus mainly affects the lungs and can cause acute respiratory distress syndrome (ARDS). In addition, coronavirus 2 severe acute respiratory syndrome (SARSCOV2) also has devastating effects on other important organs, including the circulatory system, brain, gastrointestinal tract, kidneys and liver


Author(s):  
Ernest Herbert ◽  
Dominique Fournier ◽  
Waleed A. Al-Shaqha ◽  
Mohamed Chahine

The epidemiological outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alias COVID-19, began in Wuhan, Hubei, China, in late December and eventually turned into a pandemic that has led to 3.71+ million deaths and 173+ million infected cases worldwide. In addition to respiratory manifestations, COVID-19 patients with neurological and myocardial dysfunctions exhibit a higher risk of in-hospital mortality. The immune function tends to be affected by cardiovascular risk factors and is thus indirectly related to the prognosis of COVID-19 patients. Many neurological symptoms and manifestations have been reported in COVID-19 patients. However, detailed descriptions of the prevalence and characteristic features of these symptoms are restricted due to insufficient data. It is thus advisable for clinicians to be vigilant for both cardiovascular and neurological manifestations in order to detect them at an early stage to avoid inappropriate management of COVID-19 and to address the manifestations adequately. Patients with severe COVID-19 are notably more susceptible to developing cardiovascular and neurological complications than non-severe COVID-19 patients. This review focuses on the consequential outcomes of COVID-19 on cardiovascular and neuronal functions, including other influencing factors.


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