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1.
Trials ; 22(1): 194, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: covidwho-1123665

RESUMEN

OBJECTIVES: We investigate the effects of melatonin, compared to the usual therapeutic regimen on clinical symptoms and laboratory signs in severely ill patients with confirmed COVID-19 who are admitted to the Intensive Care Unit (ICU). TRIAL DESIGN: This is a single-center, open-label, randomized, clinical trial with a parallel-group design. This study is being conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to the ICU of Shahid Mohammadi Hospital, Bandar Abbas, Iran, will be screened for the following criteria. Inclusion criteria 1. Age >20 years 2. Definitive diagnosis of COVID-19 based on RT-PCR or/and serological testing 3. Severe pneumonia and lung involvement in imaging 4. Signing informed consent Exclusion criteria 1. Underlying diseases, including convulsive disorders, chronic hepatic and renal diseases 2. Use of mechanical ventilation 3. History of known allergy to Melatonin 4. Pregnancy and breastfeeding INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin soft gelatin capsule (Danna Pharmaceutical Company) at a dose of 5 mg twice a day for a period of seven days. CONTROL GROUP: The standard treatment for COVID-19 based on the Iranian Ministry of Health and Medical Education's protocol for a period of seven days. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and checking arterial blood gas (ABG), C-reactive protein (C-RP), Ferritin, Lactate dehydrogenase (LDH) within seven days of randomization. The secondary outcomes are time to improvement of clinical and paraclinical features and length of stay in the ICU, need for mechanical ventilation, and mortality rate within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 6 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): This is an open-label trial without blinding and placebo control. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 participants randomizes (30 patients allocated to the intervention group and 30 patients allocated to the control group). TRIAL STATUS: The protocol is Version 1.0, February 16, 2021. Recruitment began February 28, 2021, and is anticipated to be completed by July 31, 2021. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N7 ". The registration date was February 16, 2021. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antioxidantes/uso terapéutico , Melatonina/uso terapéutico , Análisis de los Gases de la Sangre , Proteína C-Reactiva/metabolismo , /fisiopatología , Ferritinas/metabolismo , Humanos , Unidades de Cuidados Intensivos , Irán , L-Lactato Deshidrogenasa/metabolismo , Ensayos Clínicos Controlados Aleatorios como Asunto
2.
Int J Mol Sci ; 22(4)2021 Feb 16.
Artículo en Inglés | MEDLINE | ID: covidwho-1085070

RESUMEN

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. Throughout history, nutraceuticals, such as a variety of phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.


Asunto(s)
/tratamiento farmacológico , Suplementos Dietéticos , Melatonina/uso terapéutico , Vitaminas/uso terapéutico , Zinc/uso terapéutico , Animales , Antivirales/farmacología , Antivirales/uso terapéutico , Ácido Ascórbico/farmacología , Ácido Ascórbico/uso terapéutico , Suplementos Dietéticos/análisis , Alimentos Funcionales/análisis , Humanos , Melatonina/farmacología , Vitamina D/farmacología , Vitamina D/uso terapéutico , Vitamina E/farmacología , Vitamina E/uso terapéutico , Vitaminas/farmacología , Zinc/farmacología
3.
Vitam Horm ; 115: 67-88, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1077729

RESUMEN

Preservation of a robust circadian rhythmicity (particulsarly of the sleep/wake cycle), a proper nutrition and adequate physical exercise are key elements for healthy aging. Aging comes along with circadian alteration, e.g. a disrupted sleep and inflammation, that leads to metabolic disorders. In turn, sleep cycle disturbances cause numerous pathophysiological changes that accelerates the aging process. In the central nervous system, sleep disruption impairs several functions, among them, the clearance of waste molecules. The decrease of plasma melatonin, a molecule of unusual phylogenetic conservation present in all known aerobic organisms, plays a particular role as far as the endocrine sequels of aging. Every day, the late afternoon/nocturnal increase of melatonin synchronizes both the central circadian pacemaker located in the hypothalamic suprachiasmatic nuclei as well as myriads of peripheral cellular circadian clocks. This is called the "chronobiotic effect" of melatonin, the methoxyindole being the prototype of the endogenous family of chronobiotic agents. In addition, melatonin exerts a significant cytoprotective action by buffering free radicals and reversing inflammation via down regulation of proinflammatory cytokines, suppression of low degree inflammation and prevention of insulin resistance. Because of these properties melatonin has been advocated to be a potential therapeutic tool in COVID 19 pandemic. Melatonin administration to aged animals counteracts a significant number of senescence-related changes. In humans, melatonin is effective both as a chronobiotic and a cytoprotective agent to maintain a healthy aging. Circulating melatonin levels are consistently reduced in the metabolic syndrome, ischemic and non-ischemic cardiovascular diseases and neurodegenerative disorders like the Alzheimer's and Parkinson's diseases. The potential therapeutic value of melatonin has been suggested by a limited number of clinical trials generally employing melatonin in the 2-10mg/day range. However, from animal studies the cytoprotective effects of melatonin need higher doses to become apparent (i.e. in the 100mg/day range). Hence, controlled studies employing melatonin doses in this range are urgently needed.


Asunto(s)
Antioxidantes/farmacología , Ritmo Circadiano/efectos de los fármacos , Envejecimiento Saludable/efectos de los fármacos , Melatonina/farmacología , Animales , Antioxidantes/uso terapéutico , Humanos , Melatonina/uso terapéutico
4.
BMC Complement Med Ther ; 20(1): 353, 2020 Nov 23.
Artículo en Inglés | MEDLINE | ID: covidwho-940020

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2, and responsible for a global pandemic. Despite there being no known vaccines or medicines that prevent or cure COVID-19, many traditional, integrative, complementary and alternative medicines (TICAMs) have been touted as the solution, as well as researched as a potential remedy globally. This study presents a bibliometric analysis of global research trends at the intersection of TICAM and COVID-19. METHODS: SCOPUS, MEDLINE, EMBASE, AMED and PSYCINFO databases were searched on July 5, 2020, with results being exported on the same day. All publication types were included, however, articles were only deemed eligible if they made mention of one or more TICAMs for the potential prevention, treatment, and/or management of COVID-19 or a health issue indirectly resulting from the COVID-19 pandemic. The following eligible article characteristics were extracted: title; author names, affiliations, and countries; DOI; publication language; publication type; publication year; journal (and whether it is TICAM-focused); 2019 impact factor, and TICAMs mentioned. RESULTS: A total of 296 eligible articles were published by 1373 unique authors at 977 affiliations across 56 countries. The most common countries associated with author affiliation included China, the United States, India and Italy. The vast majority of articles were published in English, followed by Chinese. Eligible articles were published across 157 journals, of which 33 were TICAM-focused; a total of 120 journals had a 2019 impact factor, which ranged from 0.17 to 60.392. A total of 327 TICAMs were mentioned across eligible articles, with the most common ones including: traditional Chinese medicine (n = 94), vitamin D (n = 67), melatonin (n = 16), phytochemicals (n = 12), and general herbal medicine (n = 11). CONCLUSIONS: This study provides researchers and clinicians with a greater knowledge of the characteristics of articles that been published globally at the intersection of COVID-19 and TICAM to date. At a time where safe and effective vaccines and medicines for the prevention and treatment of COVID-19 have yet to be discovered, this study provides a current snapshot of the quantity and characteristics of articles written at the intersection of TICAM therapies and COVID-19.


Asunto(s)
Investigación Biomédica , Infecciones por Coronavirus/tratamiento farmacológico , Medicina Integral , Medicina China Tradicional , Pandemias , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , Bibliometría , Investigación Biomédica/tendencias , China/epidemiología , Terapias Complementarias , Coronavirus , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Bases de Datos Factuales , Medicamentos Herbarios Chinos , Humanos , India/epidemiología , Italia/epidemiología , Melatonina/uso terapéutico , Fitoterapia , Neumonía Viral/epidemiología , Neumonía Viral/virología , Edición , Estados Unidos/epidemiología , Vitamina D/uso terapéutico
5.
Trials ; 21(1): 882, 2020 Oct 26.
Artículo en Inglés | MEDLINE | ID: covidwho-892369

RESUMEN

OBJECTIVES: We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. INCLUSION CRITERIA: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. CONTROL GROUP: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1ß (IL-1ß), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients randomized into two groups (30 in each group). TRIAL STATUS: The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N5 ". The registration date was 14 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Betacoronavirus/efectos de los fármacos , Depresores del Sistema Nervioso Central/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Melatonina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adulto , Betacoronavirus/genética , Biomarcadores/sangre , Estudios de Casos y Controles , Depresores del Sistema Nervioso Central/administración & dosificación , Depresores del Sistema Nervioso Central/efectos adversos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Método Doble Ciego , Hospitalización , Humanos , Irán/epidemiología , Melatonina/administración & dosificación , Melatonina/efectos adversos , Oxígeno/sangre , Pandemias , Placebos/administración & dosificación , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Seguridad , Factores de Tiempo , Resultado del Tratamiento
6.
J Pineal Res ; 69(3): e12676, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: covidwho-620325

RESUMEN

Melatonin is a chronobiotic hormone, which can regulate human diseases like cancer, atherosclerosis, respiratory disorders, and microbial infections by regulating redox system. Melatonin exhibits innate immunomodulation by communicating with immune system and influencing neutrophils to fight infections and inflammation. However, sustaining redox homeostasis and reactive oxygen species (ROS) generation in neutrophils are critical during chemotaxis, oxidative burst, phagocytosis, and neutrophil extracellular trap (NET) formation. Therefore, endogenous antioxidant glutathione (GSH) redox cycle is highly vital in regulating neutrophil functions. Reduced intracellular GSH levels and glutathione reductase (GR) activity in the neutrophils during clinical conditions like autoimmune disorders, neurological disorders, diabetes, and microbial infections lead to dysfunctional neutrophils. Therefore, we hypothesized that redox modulators like melatonin can protect neutrophil health and functions under GSH and GR activity-deficient conditions. We demonstrate the dual role of melatonin, wherein it protects neutrophils from oxidative stress-induced apoptosis by reducing ROS generation; in contrast, it restores neutrophil functions like phagocytosis, degranulation, and NETosis in GSH and GR activity-deficient neutrophils by regulating ROS levels both in vitro and in vivo. Melatonin mitigates LPS-induced neutrophil dysfunctions by rejuvenating GSH redox system, specifically GR activity by acting as a parallel redox system. Our results indicate that melatonin could be a potential auxiliary therapy to treat immune dysfunction and microbial infections, including virus, under chronic disease conditions by restoring neutrophil functions. Further, melatonin could be a promising immune system booster to fight unprecedented pandemics like the current COVID-19. However, further studies are indispensable to address the clinical usage of melatonin.


Asunto(s)
Antioxidantes/uso terapéutico , Glutatión/metabolismo , Melatonina/uso terapéutico , Neutrófilos/efectos de los fármacos , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Femenino , Glutatión Reductasa/metabolismo , Humanos , Masculino , Melatonina/farmacología , Ratones , Mitocondrias/metabolismo , NADPH Oxidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
7.
Mol Biol Rep ; 47(10): 8229-8233, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: covidwho-754391

RESUMEN

COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.


Asunto(s)
Adyuvantes Farmacéuticos/uso terapéutico , Antivirales/uso terapéutico , Basigina/metabolismo , Infecciones por Coronavirus/tratamiento farmacológico , Melatonina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Animales , Antioxidantes/metabolismo , Antivirales/farmacología , Basigina/antagonistas & inhibidores , Infecciones por Coronavirus/metabolismo , Humanos , Sistema Inmunológico/efectos de los fármacos , Melatonina/farmacología , Pandemias , Neumonía Viral/metabolismo , Transducción de Señal/efectos de los fármacos
9.
Nutrients ; 12(9)2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: covidwho-727437

RESUMEN

The recent pandemic of COVID-19 has already infected millions of individuals and has resulted in the death of hundreds of thousands worldwide. Based on clinical features, pathology, and the pathogenesis of respiratory disorders induced by this and other highly homogenous coronaviruses, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response contribute to COVID-19 pathology; these are caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This leads to a cytokine storm and subsequent progression triggering acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), and often death. We and others have reported melatonin to be an anti-inflammatory and anti-oxidative molecule with a high safety profile. It is effective in critical care patients by reducing their vascular permeability and anxiety, inducing sedation, and improving their quality of sleep. As melatonin shows no harmful adverse effects in humans, it is imperative to introduce this indoleamine into clinical trials where it might be beneficial for better clinical outcomes as an adjuvant treatment of COVID-19-infected patients. Herein, we strongly encourage health care professionals to test the potential of melatonin for targeting the COVID-19 pandemic. This is urgent, since there is no reliable treatment for this devastating disease.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Melatonina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/virología , Humanos , Pandemias , Neumonía Viral/virología
10.
Psychosomatics ; 61(6): 585-596, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-726823

RESUMEN

BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the biggest health threats of our generation. A significant portion of patients are presenting with delirium and neuropsychiatric sequelae of the disease. Unique examination findings and responses to treatment have been identified. OBJECTIVE: In this article, we seek to provide pharmacologic and treatment recommendations specific to delirium in patients with COVID-19. METHODS: We performed a literature search reviewing the neuropsychiatric complications and treatments in prior coronavirus epidemics including Middle Eastern respiratory syndrome and severe acute respiratory syndrome coronaviruses, as well as the emerging literature regarding COVID-19. We also convened a work group of consultation-liaison psychiatrists actively managing patients with COVID-19 in our hospital. Finally, we synthesized these findings to provide preliminary pharmacologic recommendations for treating delirium in these patients. RESULTS: Delirium is frequently found in patients who test positive for COVID-19, even in the absence of respiratory symptoms. There appears to be a higher rate of agitation, myoclonus, abulia, and alogia. No data are currently available on the treatment of delirium in patients with COVID-19. Extrapolating from general delirium treatment, Middle Eastern respiratory syndrome/severe acute respiratory syndrome case reports, and our experience, preliminary recommendations for pharmacologic management have been assembled. CONCLUSIONS: COVID-19 is associated with neuropsychiatric symptoms. Low-potency neuroleptics and alpha-2 adrenergic agents may be especially useful in this setting. Further research into the pathophysiology of COVID-19 will be key in developing more targeted treatment guidelines.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Antipsicóticos/uso terapéutico , Encefalopatías/fisiopatología , Infecciones por Coronavirus/fisiopatología , Delirio/tratamiento farmacológico , Agonistas de Dopamina/uso terapéutico , Neumonía Viral/fisiopatología , Betacoronavirus , Encefalopatías/psicología , Depresores del Sistema Nervioso Central/uso terapéutico , Infecciones por Coronavirus/psicología , Delirio/fisiopatología , Delirio/psicología , Moduladores del GABA/uso terapéutico , Humanos , Lorazepam/uso terapéutico , Melatonina/uso terapéutico , Pandemias , Neumonía Viral/psicología , Guías de Práctica Clínica como Asunto
11.
Biomolecules ; 10(9)2020 08 20.
Artículo en Inglés | MEDLINE | ID: covidwho-724198

RESUMEN

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.


Asunto(s)
Adyuvantes Farmacéuticos/uso terapéutico , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Melatonina/administración & dosificación , Melatonina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Adyuvantes Farmacéuticos/administración & dosificación , Adyuvantes Farmacéuticos/farmacología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Homeostasis/efectos de los fármacos , Humanos , Melatonina/farmacología , Pandemias
12.
Int J Med Sci ; 17(14): 2133-2146, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-719845

RESUMEN

The SARS-CoV-2 spread quickly across the globe. The World Health Organization (WHO) on March 11 declared COVID-19 a pandemic. The mortality rate, hospital disorders and incalculable economic and social damages, besides the unproven efficacy of the treatments evaluated against COVID-19, raised the need for immediate control of this disease. Therefore, the current study employed in silico tools to rationally identify new possible SARS-CoV-2 main protease (Mpro) inhibitors. That is an enzyme conserved among the coronavirus species; hence, the identification of an Mpro inhibitor is to make it a broad-spectrum drug. Molecular docking studies described the binding sites and the interaction energies of 74 Mpro-ligand complexes deposited in the Protein Data Bank (PDB). A structural similarity screening was carried out in order to identify possible Mpro ligands that show additional pharmacological properties against COVID-19. We identified 59 hit compounds and among them, melatonin stood out due to its prominent immunomodulatory and anti-inflammatory activities; it can reduce oxidative stress, defence cell mobility and efficiently combat the cytokine storm and sepsis. In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. Interestingly, one of the most promising hits in our docking study was melatonin. It revealed better interaction energy with Mpro compared to ligands in complexes from PDB. Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation. These results definitely do not confirm antiviral activity, but can rather be used as a basis for further preclinical and clinical trials.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Descubrimiento de Drogas , Melatonina/farmacología , Neumonía Viral/tratamiento farmacológico , Proteínas no Estructurales Virales/antagonistas & inhibidores , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/virología , Cisteína Endopeptidasas , Humanos , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Melatonina/uso terapéutico , Simulación del Acoplamiento Molecular , Pandemias , Neumonía Viral/virología , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/uso terapéutico
13.
Turk J Med Sci ; 50(6): 1504-1512, 2020 10 22.
Artículo en Inglés | MEDLINE | ID: covidwho-709719

RESUMEN

The aim of this review is to summarize current studies on the relationship between melatonin and aging. Nowadays, age-related diseases come into prominence, and identifying age-related changes and developing proper therapeutic approaches are counted as some of the major issues regarding community health. Melatonin is the main hormone of the pineal gland. Melatonin is known to influence many biological processes in the body, including circadian rhythms, the immune system, and neuroendocrine and cardiovascular functions.Melatoninrhythms also reflect the biological process of aging. Aging is an extremely complex and multifactorial process. Melatonin levels decline considerably with aging and its decline is associated with several age-related diseases. Aging is closely associated with oxidative damage and mitochondrial dysfunction. Free radical reactions initiated by the mitochondria constitute the inherent aging process. Melatonin plays a pivotal role in preventing age-related oxidative stress. Coronavirus disease 2019 (COVID-19) fatality rates increase with chronic diseases and age, where melatonin levels decrease. For this reason, melatonin supplementation in elderly could be beneficial in COVID-19 treatment. Therefore, studies on the usage of melatonin in COVID-19 treatment are needed.


Asunto(s)
Envejecimiento , Antioxidantes/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Melatonina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Neumonía Viral/tratamiento farmacológico , Anciano , Envejecimiento/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Betacoronavirus , Infecciones por Coronavirus/virología , Suplementos Dietéticos , Humanos , Melatonina/metabolismo , Melatonina/farmacología , Pandemias , Neumonía Viral/virología
14.
Virus Res ; 287: 198108, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: covidwho-694184

RESUMEN

Viral infections are dangerous diseases for human health worldwide, which lead to significant morbidity and mortality each year. Because of their importance and the lack of effective therapeutic approaches, further attempts should be made to discover appropriate alternative or complementary treatments. Melatonin, a multifunctional neurohormone mainly synthesized and secreted by the pineal gland, plays some roles in the treatment of viral infections. Regarding a deadly outbreak of COVID-19 across the world, we decided to discuss melatonin functions against various viral infections including COVID-19. Therefore, in this review, we summarize current evidence on melatonin therapy for viral infections with focus on possible underlying mechanisms of melatonin actions.


Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/virología , Melatonina/farmacología , Neumonía Viral/virología , Antioxidantes , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/metabolismo , Interacciones Huésped-Patógeno , Humanos , Melatonina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Neumonía Viral/metabolismo , Transducción de Señal/efectos de los fármacos , Vacunación , Vacunas Virales/administración & dosificación , Vacunas Virales/inmunología , Virosis/tratamiento farmacológico , Virosis/metabolismo , Virosis/virología
15.
Eur J Pharmacol ; 882: 173329, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: covidwho-626109

RESUMEN

Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a newly discovered highly pathogenic virus that was declared pandemic in March 2020 by the World Health Organization. The virus affects the respiratory system, produces an inflammatory storm that causes lung damage and respiratory dysfunction. It infects humans of all ages. The Covid-19 takes a more severe course in individuals with chronic metabolic diseases such as obesity, diabetes mellitus, and hypertension. This category of persons exhibits weak immune activity and decreased levels of endogenous antioxidants. Melatonin is a multifunctional signaling hormone synthesized and secreted primarily by the pineal gland. It is a potent antioxidant with immunomodulatory action and has remarkable anti-inflammatory effects under a variety of circumstances. Regarding Covid-19 and metabolic syndrome, adequate information about the relationship between these two comorbidities is required for better management of these patients. Since Covid-19 infection and complications involve severe inflammation and oxidative stress in people with obesity and diabetes, we anticipated the inclusion of melatonin, as powerful antioxidant, within proposed treatment protocols. In this context, melatonin is a potential and promising agent to help overcome Covid-19 infection and boost the immune system in healthy persons and obese and diabetic patients. This review summarizes some evidence from recently published reports on the utility of melatonin as a potential adjuvant in Covid-19-infected individuals with diabetes and obesity.


Asunto(s)
Betacoronavirus/inmunología , Infecciones por Coronavirus/tratamiento farmacológico , Diabetes Mellitus/inmunología , Melatonina/farmacología , Obesidad/inmunología , Neumonía Viral/tratamiento farmacológico , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Betacoronavirus/patogenicidad , Ensayos Clínicos como Asunto , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Diabetes Mellitus/epidemiología , Interacciones Microbiota-Huesped/efectos de los fármacos , Interacciones Microbiota-Huesped/inmunología , Humanos , Sistema Inmunológico/efectos de los fármacos , Pulmón , Melatonina/uso terapéutico , Obesidad/epidemiología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/virología , Factores de Riesgo , Resultado del Tratamiento
16.
Psychosomatics ; 61(5): 544-550, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-616923

Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Antipsicóticos/uso terapéutico , Infecciones por Coronavirus/terapia , Delirio/tratamiento farmacológico , Hipnóticos y Sedantes/efectos adversos , Neumonía Viral/terapia , Agitación Psicomotora/tratamiento farmacológico , Fármacos Inductores del Sueño/uso terapéutico , Anciano , Analgésicos Opioides/efectos adversos , Azepinas/uso terapéutico , Betacoronavirus , Depresores del Sistema Nervioso Central/uso terapéutico , Clordiazepóxido/efectos adversos , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/psicología , Delirio/etiología , Delirio/fisiopatología , Delirio/psicología , Dexmedetomidina/efectos adversos , Femenino , Guanfacina/uso terapéutico , Haloperidol/uso terapéutico , Humanos , Hidromorfona/efectos adversos , Unidades de Cuidados Intensivos , Ketamina/efectos adversos , Melatonina/uso terapéutico , Midazolam/efectos adversos , Oxicodona/efectos adversos , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/fisiopatología , Neumonía Viral/psicología , Propofol/efectos adversos , Agitación Psicomotora/etiología , Agitación Psicomotora/fisiopatología , Agitación Psicomotora/psicología , Respiración Artificial , Trastornos del Sueño del Ritmo Circadiano/tratamiento farmacológico , Trastornos del Sueño del Ritmo Circadiano/etiología , Trastornos del Sueño del Ritmo Circadiano/fisiopatología , Traqueostomía , Triazoles/uso terapéutico , Ácido Valproico/uso terapéutico
17.
Int Arch Allergy Immunol ; 181(8): 629-634, 2020.
Artículo en Inglés | MEDLINE | ID: covidwho-610697

RESUMEN

The difference between the female and male immune response to COVID-19 infection, and infections in general, is multifactorial. The well-known determiners of the immune response, such as X and Y chromosomes, sex hormones, and microbiota, are functionally interconnected and influence each other in shaping the organism's immunity. We focus our commentary on the interplay between the genetic sex and mitochondria and how this may affect a sex-dependent immune response in COVID-19 infection. Realizing the existence of these interactions may help in designing novel methods or fine-tuning the existing and routine therapies to fight COVID-19 and other infections.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/inmunología , Mitocondrias/fisiología , Neumonía Viral/inmunología , Cromosomas Sexuales/fisiología , Infecciones por Coronavirus/tratamiento farmacológico , Femenino , Humanos , Masculino , Melatonina/uso terapéutico , Pandemias , Neumonía Viral/tratamiento farmacológico , Caracteres Sexuales
18.
Life Sci ; 254: 117808, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: covidwho-276422

RESUMEN

COVID-19 pandemic has a high mortality rate and is affecting practically the entire world population. The leading cause of death is severe acute respiratory syndrome as a consequence of exacerbated inflammatory response accompanied by uncontrolled oxidative stress as well as the inflammatory reaction at the lung level. Until now, there is not a specific and definitive treatment for this pathology that worries the world population, especially the older adults who constitute the main risk group. In this context, it results in a particular interest in the evaluation of the efficacy of existing pharmacological agents that may be used for overcoming or attenuating the severity of this pulmonary complication that has ended the lives of many people worldwide. Vitamin D and melatonin could be good options for achieving this aim, taking into account that they have many shared underlying mechanisms that are able to modulate and control the immune adequately and oxidative response against COVID-19 infection, possibly even through a synergistic interaction. The renin-angiotensin system exaltation with consequent inflammatory response has a leading role in the physiopathology of COVID-19 infection; and it may be down-regulated by vitamin D and melatonin in many organs. Therefore, it is also essential to analyze this potential therapeutic association and their relation with RAS as part of this new approach.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Pulmón/virología , Melatonina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Vitamina D/uso terapéutico , Antioxidantes , Betacoronavirus , Infecciones por Coronavirus/patología , Humanos , Inflamación , Pandemias , Neumonía Viral/patología , Sistema Renina-Angiotensina
20.
Life Sci ; 250: 117583, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: covidwho-12003

RESUMEN

This article summarizes the likely benefits of melatonin in the attenuation of COVID-19 based on its putative pathogenesis. The recent outbreak of COVID-19 has become a pandemic with tens of thousands of infected patients. Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. This leads to a cytokine storm and subsequent progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and often death. Melatonin, a well-known anti-inflammatory and anti-oxidative molecule, is protective against ALI/ARDS caused by viral and other pathogens. Melatonin is effective in critical care patients by reducing vessel permeability, anxiety, sedation use, and improving sleeping quality, which might also be beneficial for better clinical outcomes for COVID-19 patients. Notably, melatonin has a high safety profile. There is significant data showing that melatonin limits virus-related diseases and would also likely be beneficial in COVID-19 patients. Additional experiments and clinical studies are required to confirm this speculation.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Melatonina/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/inmunología , Lesión Pulmonar Aguda/virología , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Betacoronavirus , Citocinas/inmunología , Humanos , Inmunomodulación , Inflamación/tratamiento farmacológico , Pandemias , /virología
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