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1.
Int J Mol Sci ; 23(7)2022 Mar 25.
Article in English | MEDLINE | ID: covidwho-1785729

ABSTRACT

The development of affordable, effective, and environmentally friendly barrier fabrics is a current goal in antimicrobial textile development. The discovery of new routes to achieve non-toxic naturally occurring molecules with antimicrobial activity is of interest in the development of materials that promote wound healing, improve hygiene, and offer protection against nosocomial infection. Highly cleaned and sterile unbleached cotton has constituents that produce hydrogen peroxide at levels commensurate with those that favor cell signaling in wound healing. Here, we show the antimicrobial and antiviral properties of spunlaced griege cotton-containing nonwovens treated with ascorbic acid formulations. The mechanism of action occurs through the promotion of enhanced hydrogen peroxide activity. The levels of hydrogen peroxide activity afford antimicrobial activity against Gram-negative and Gram-positive bacteria and antiviral activity against MS2 bacteriophages. Spun-bond nonwoven unbleached cotton was treated with ascorbic acid using traditional pad-dry-cure methods. An assessment of antibacterial and antiviral activity against Staphylococcus aureus, Klebsiella pneumoniae, and MS2 bacteriophages with the AATCC 100 test method showed a 99.99% inhibitory activity. An approach to the covalent attachment of ascorbic to cellulose through citric acid crosslinking chemistry is also discussed. Thus, a simple, low-cost approach to antimicrobial and antiviral cotton-based nonwovens applicable to dressings, nosocomial barrier fabrics, and face masks can be adopted by combining ascorbic acid with spunlace greige cotton nonwoven fabrics.


Subject(s)
Anti-Infective Agents , Cotton Fiber , Adjuvants, Pharmaceutic , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antiviral Agents , Ascorbic Acid/pharmacology , Gossypium , Hydrogen Peroxide , Textiles
2.
Complement Ther Med ; 67: 102827, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1768027

ABSTRACT

OBJECTIVES: With the expansion of the internet, social media platforms have become a major source of medical information. However, medical information on online multimedia platforms is often inaccurate. In the current study, we evaluated the reliability, quality, and accuracy of the most viewed YouTube videos featuring the effects of vitamin C on COVID-19. METHODS: A search was conducted on YouTube on January 13, 2022, using the keywords ("ascorbic acid" OR "vitamin C" OR "sodium ascorbate" OR "L-ascorbic") AND ("coronavirus" OR "COVID 19" OR "COVID-19" OR "Corona" OR "COVID" OR "SARSCoV2"). We assessed the 50 most-viewed videos using a modified DISCERN scale (mDISCERN) and Global Quality Scale (GQS). Additionally, the accuracy of the information in each video was evaluated. RESULTS: Out of the 50 most-viewed videos featuring the effect of vitamin C on COVID-19, 54% were not reliable. Furthermore, 62% presented poor quality, and 74% were misleading or neither accurate nor misleading. The average mDISCERN and GQS scores of the 50 included videos were 2.2 ± 1.4 (≥ 3: highly reliable) and 2.2 ± 1.1 (2: generally poor), respectively. Although the videos were made by medical doctors, their reliability, quality, and accuracy were not significantly different from those displayed in other sources, including fitness channels, television or internet-based news or programs, consumers, company channels, product advertisements, or prepared by nurses. CONCLUSIONS: The reliability, quality, and accuracy of the 50 most-viewed videos on the effect of vitamin C on COVID-19 were not high. Video creators, especially medical doctors, should make an effort so that the videos present reliable content with high-quality and correct information is disseminated to people.


Subject(s)
COVID-19 , Social Media , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , COVID-19/drug therapy , Humans , Information Dissemination , Reproducibility of Results , Video Recording
3.
Libyan J Med ; 17(1): 2054111, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1752028

ABSTRACT

Vitamins (Vit) C and D are widely used as immunogenic supplements among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. The SAR-CoV-2 virus enters into the pulmonary endothelial cells through attachment to angiotensin converting enzyme 2 receptor (Ace2) and the proteolytic activity of Cathepsin L (Ctsl) and transmembrane serine protease 2 (Tmprss2) enzymes. This study aimed to determine the influence of Vit C and D on the mRNA expression of Ace2, Tmprss2, and Ctsl genes in the mouse lungs. Vitamins C and D were administrated to different groups of mice through intra-peritoneal route in doses equivalent to human for 30 days. Then, the mRNA expression of SARS-CoV-2 entry gene was analyzed using qRT-PCR. It is found that Vit D, but not C, upregulated significantly (P < 0.05) the mRNA expression of Ace2 by more than six folds, while downregulated the expression of Ctsl and Tmprss2 genes by 2.8 and 2.2 folds, respectively. It can be concluded from this study that Vit D alters the mRNA expression of Ace2, Tmprss, and Ctsl genes in the mouse lungs. This finding can help us in understanding, at least in part, the molecular influence of Vit D on genes involved in the entry of SARS-CoV-2 into the cells.


Subject(s)
COVID-19 , Serine Proteases , Angiotensin-Converting Enzyme 2 , Animals , Ascorbic Acid/metabolism , Ascorbic Acid/pharmacology , Cathepsin L/genetics , Cathepsin L/metabolism , Endothelial Cells , Humans , Lung/metabolism , Mice , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , RNA, Messenger/metabolism , SARS-CoV-2 , Serine Proteases/metabolism , Vitamins
4.
Cardiovasc Hematol Disord Drug Targets ; 21(4): 235-242, 2021.
Article in English | MEDLINE | ID: covidwho-1573714

ABSTRACT

AIMS: The study aimed to assess the inhibitory effect of Vitamin C on angiotensin-converting enzyme 2. BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses angiotensin-converting enzyme 2 (ACE-II) as the first route to infect human cells. Accordingly, agents with potential inhibition of ACE-II receptors might be effective in the prevention and management of COVID-19. OBJECTIVE: The goal of this work was to assess the possible inhibitory effect of ACE-II on ascorbic acid using an ex vivo approach based on the inhibition of diminazene-induced vasorelaxation. MATERIALS AND METHODS: In the present study, diminazene was used as a known specific inhibitor of ACE-II. Then, the vasorelaxant effect of ascorbic acid on diminazene-induced relaxation was examined using isolated aortic rings. All experiments of this study were evaluated on isolated aortic rings precontracted by epinephrine. RESULTS: The results confirmed that diminazene-induced vasorelaxation in a dose-dependent manner. More interestingly, ascorbic acid inhibited diminazene-induced vasorelaxation in a dose-dependent manner. CONCLUSION: This investigation provides valuable experimental proof of the efficacy of ascorbic acid (Vitamin C) on inhibiting ex vivo vascular angiotensin-converting enzyme II, which is known among the pharmacological targets of anti-COVID-19 drugs.


Subject(s)
Ascorbic Acid , COVID-19 , Angiotensin-Converting Enzyme 2 , Angiotensins , Animals , Ascorbic Acid/pharmacology , Humans , Rats , SARS-CoV-2
5.
Semin Respir Crit Care Med ; 42(5): 672-682, 2021 10.
Article in English | MEDLINE | ID: covidwho-1493295

ABSTRACT

While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 µmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.


Subject(s)
Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Shock, Septic/drug therapy , Vitamins/pharmacology , Vitamins/therapeutic use , Animals , Antioxidants/pharmacology , Ascorbic Acid/administration & dosage , Ascorbic Acid/adverse effects , Ascorbic Acid Deficiency/physiopathology , Clinical Trials as Topic , Critical Illness , Dose-Response Relationship, Drug , Glucocorticoids/pharmacology , Humans , Inflammation Mediators/metabolism , Vasoconstrictor Agents/pharmacology , Vitamins/administration & dosage , Vitamins/adverse effects
6.
Nutrients ; 13(10)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1477977

ABSTRACT

BACKGROUND: Vitamin C is a water-soluble antioxidant vitamin. Oxidative stress and its markers, along with inflammatory markers, are high during critical illness. Due to conflicting results of the published literature regarding the efficacy of vitamin C in critically ill patients, and especially the concerns for nephrotoxicity raised by some case reports, this meta-analysis was carried out to appraise the evidence and affirmation regarding the role of vitamin C in critically ill patients. METHODS: We searched the database thoroughly to collect relevant studies that assessed intravenous vitamin C use in critically ill patients published until 25 February 2021. We included randomized controlled trials and observational studies with 20 or more critically ill patients who have received intravenous ascorbic acid (vitamin C). After screening 18,312 studies from different databases, 53 were included in our narrative synthesis, and 48 were included in the meta-analysis. We used the Covidence software for screening of the retrieved literature. Review Manager (RevMan) 5.4 was used for the pooling of data and Odds Ratios (OR) and Mean difference (MD) as measures of effects with a 95% confidence interval to assess for explanatory variables. RESULTS: Pooling data from 33 studies for overall hospital mortality outcomes using a random-effect model showed a 19% reduction in odds of mortality among the vitamin C group (OR, 0.81; 95% CI, 0.66-0.98). Length of hospital stay (LOS), mortality at 28/30 days, ICU mortality, new-onset AKI and Renal Replacement Therapy (RRT) for AKI did not differ significantly across the two groups. Analysis of data from 30 studies reporting ICU stay disclosed 0.76 fewer ICU days in the vitamin C group than the placebo/standard of care (SOC) group (95% CI, -1.34 to -0.19). This significance for shortening ICU stay persisted even when considering RCTs only in the analysis (MD, -0.70; 95% CI, -1.39 to -0.02). CONCLUSION: Treatment of critically ill patients with intravenous vitamin C was relatively safe with no significant difference in adverse renal events and decreased in-hospital mortality. The use of vitamin C showed a significant reduction in the length of ICU stays in critically ill patients.


Subject(s)
Ascorbic Acid/pharmacology , Critical Illness , Acute Kidney Injury/therapy , Clinical Trials as Topic , Critical Illness/mortality , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Renal Replacement Therapy
7.
Pharmacol Res ; 169: 105665, 2021 07.
Article in English | MEDLINE | ID: covidwho-1433725

ABSTRACT

Previous studies have reported that vitamin C supplementation may decrease lipid profile in patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the influence of vitamin C supplementation on lipid profile in patients with T2DM. Studies examining the effects of vitamin C supplementation on lipid profile in patients with T2DM, published up to November 2020, were identified through PubMed, SCOPUS, and Embase databases. 15 studies, including 872 participants, were included and analyzed using a random-effects model to calculate weighted mean differences (WMDs) with 95% confidence intervals (CI). Findings from 15 studies indicated that vitamin C supplementation significantly decreased Triglyceride (TG) (WMD: -16.48 mg/dl, 95% CI (-31.89, -1.08), P < 0.001) and total cholesterol (TC) (WMD: -13.00 mg/dl, 95% CI (-23.10, -2.91), P < 0.001) in patients with T2DM. However, vitamin C supplementation failed to improve LDL and HDL. The meta-regression analysis suggested that lipid profile improvement was affected by duration of vitamin C treatment. Dose-response analysis showed that vitamin C supplementation changed LDL significantly based on vitamin C dose. According to our findings, vitamin C supplementation significantly improved lipid profile via decreases in TG and TC. However, vitamin C failed to affect LDL and HDL in diabetic populations. It appears that vitamin C supplementation is more beneficial to lipid profile in long-term vs. short term interventions.


Subject(s)
Ascorbic Acid/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Lipids/blood , Ascorbic Acid/administration & dosage , Ascorbic Acid/pharmacology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Dietary Supplements , Dose-Response Relationship, Drug , Humans , Lipid Metabolism/drug effects
8.
FASEB J ; 35(6): e21651, 2021 06.
Article in English | MEDLINE | ID: covidwho-1388031

ABSTRACT

The SARS-CoV-2 pandemic imposed a large burden on health and society. Therapeutics targeting different components and processes of the viral infection replication cycle are being investigated, particularly to repurpose already approved drugs. Spike protein is an important target for both vaccines and therapeutics. Insights into the mechanisms of spike-ACE2 binding and cell fusion could support the identification of compounds with inhibitory effects. Here, we demonstrate that the integrity of disulfide bonds within the receptor-binding domain (RBD) plays an important role in the membrane fusion process although their disruption does not prevent binding of spike protein to ACE2. Several reducing agents and thiol-reactive compounds are able to inhibit viral entry. N-acetyl cysteine amide, L-ascorbic acid, JTT-705, and auranofin prevented syncytia formation, viral entry into cells, and infection in a mouse model, supporting disulfides of the RBD as a therapeutically relevant target.


Subject(s)
Acetylcysteine/analogs & derivatives , Amides/pharmacology , Ascorbic Acid/pharmacology , Auranofin/pharmacology , COVID-19 , Disulfides/metabolism , Esters/pharmacology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Sulfhydryl Compounds/pharmacology , Virus Internalization/drug effects , Acetylcysteine/pharmacology , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/pathology , HEK293 Cells , Humans
9.
Nutrients ; 13(4)2021 Mar 27.
Article in English | MEDLINE | ID: covidwho-1383900

ABSTRACT

Vitamin C (ascorbic acid) is a normal liver metabolite in most animals, with humans being a notable exception due to random genetic mutations that have occurred during our evolution [...].


Subject(s)
Ascorbic Acid/administration & dosage , Ascorbic Acid/pharmacology , Ascorbic Acid/pharmacokinetics , Bacterial Infections/drug therapy , COVID-19/drug therapy , COVID-19/virology , Epigenesis, Genetic , Humans , Neoplasms/drug therapy , SARS-CoV-2 , Sepsis/drug therapy
10.
Biomed Pharmacother ; 142: 111956, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330661

ABSTRACT

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90-95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored.


Subject(s)
COVID-19/drug therapy , Cannabidiol/pharmacology , SARS-CoV-2 , Antiviral Agents/pharmacology , Ascorbic Acid/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , Dietary Supplements , Doxycycline/pharmacology , Drug Repositioning/methods , Drug Therapy, Combination/methods , Humans , Ivermectin , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Treatment Outcome , Vitamin D/pharmacology , Zinc/pharmacology
11.
Biomed Pharmacother ; 141: 111823, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1272313

ABSTRACT

Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.


Subject(s)
Ascorbic Acid/chemistry , Ascorbic Acid/therapeutic use , Magnesium Sulfate/chemistry , Magnesium Sulfate/therapeutic use , Niacinamide/chemistry , Niacinamide/therapeutic use , Pantothenic Acid/chemistry , Pantothenic Acid/therapeutic use , Pyridoxine/chemistry , Pyridoxine/therapeutic use , Riboflavin/chemistry , Riboflavin/therapeutic use , Sepsis/drug therapy , Sepsis/metabolism , Thiamine/chemistry , Thiamine/therapeutic use , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/therapeutic use , Ascorbic Acid/pharmacology , Dogs , Dose-Response Relationship, Drug , Drug Combinations , Drug Compounding , Female , Humans , Lipopolysaccharides/toxicity , Magnesium Sulfate/pharmacology , Male , Mice , Mice, Inbred BALB C , Niacinamide/pharmacology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Pantothenic Acid/pharmacology , Pyridoxine/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Riboflavin/pharmacology , Sepsis/pathology , Superoxide Dismutase/metabolism , Thiamine/pharmacology
12.
Clin Nutr ESPEN ; 43: 39-48, 2021 06.
Article in English | MEDLINE | ID: covidwho-1157201

ABSTRACT

BACKGROUND: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.


Subject(s)
COVID-19/drug therapy , Dietary Supplements , Fatty Acids, Omega-3/therapeutic use , Immunologic Factors/therapeutic use , Trace Elements/therapeutic use , Vitamins/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , COVID-19/immunology , Comorbidity , Fatty Acids, Omega-3/pharmacology , Female , Humans , Immunologic Factors/pharmacology , Male , Micronutrients/pharmacology , Micronutrients/therapeutic use , Nutritional Status , Pandemics , Pregnancy , SARS-CoV-2 , Selenium/pharmacology , Selenium/therapeutic use , Switzerland , Trace Elements/pharmacology , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamins/pharmacology , Zinc/pharmacology , Zinc/therapeutic use
13.
Int J Mol Sci ; 22(4)2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1085070

ABSTRACT

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.


Subject(s)
COVID-19/drug therapy , Dietary Supplements , Melatonin/therapeutic use , Vitamins/therapeutic use , Zinc/therapeutic use , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Dietary Supplements/analysis , Functional Food/analysis , Humans , Melatonin/pharmacology , SARS-CoV-2/drug effects , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamin E/pharmacology , Vitamin E/therapeutic use , Vitamins/pharmacology , Zinc/pharmacology
14.
J Pharm Biomed Anal ; 196: 113927, 2021 Mar 20.
Article in English | MEDLINE | ID: covidwho-1051794

ABSTRACT

To administer vitamin C (VC) with precision to patients with the coronavirus disease (COVID-19), we developed an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess plasma VC concentrations. 31 patients with COVID-19 and 51 healthy volunteers were enrolled. VC stability was evaluated in blood, plasma, and precipitant-containing stabilizers. A proportion of 7.7 % of VC was degraded in blood at room temperature (RT) (approximately 20-25 °C) at 1.5 h post administration with respect to the proportion degraded at 0.5 h, but without statistical difference. VC was stable in plasma for 0.75 h at RT, 2 h at 4 °C, 5 days at -40 °C, and 4 h in precipitant-containing stabilizer (2 % oxalic acid) at RT. The mean plasma concentration of VC in patients with COVID-19 was 2.00 mg/L (0.5-4.90) (n = 8), which was almost 5-fold lower than that in healthy volunteers (9.23 mg/L (3.09. 35.30)) (n = 51). After high-dose VC treatment, the mean VC concentration increased to 13.46 mg/L (3.93. 34.70) (n = 36), higher than that in healthy volunteers, and was within the normal range (6-20 mg/L). In summary, we developed a simple UPLC-MS/MS method to quantify VC in plasma, and determined the duration for which the sample remained stable. VC levels in patients with COVID-19 were considerably low, and supplementation at 100 mg/kg/day is considered highly essential.


Subject(s)
Ascorbic Acid/blood , Ascorbic Acid/pharmacology , COVID-19/blood , COVID-19/prevention & control , Adult , Aged , Chromatography, High Pressure Liquid/methods , Dietary Supplements , Female , Humans , Male , Middle Aged , Plasma/chemistry , Reference Values , SARS-CoV-2/pathogenicity , Tandem Mass Spectrometry/methods , Young Adult
15.
Virology ; 555: 10-18, 2021 03.
Article in English | MEDLINE | ID: covidwho-1003121

ABSTRACT

Novel coronavirus (SARS-CoV-2), turned out to be a global pandemic with unstoppable morbidity and mortality rate. However, till date there is no effective treatment found against SARS-CoV-2. We report on the major in-depth molecular and docking analysis by using antiretroviral (Lopinavir and ritonavir), antimalarial (Hydroxychloroquine), antibiotics (Azithromycin), and dietary supplements (Vitamin C and E) to provide new insight into drug repurposing molecular events involved in SARS-CoV-2. We constructed three drug-target-pathways-disease networks to predict the targets and drugs interactions as well as important pathways involved in SARS-CoV-2. The results suggested that by using the combination of Lopinavir, Ritonavir along with Hydroxychloroquine and Vitamin C may turned out to be the effective line of treatment for SARS-CoV-2 as it shows the involvement of PARP-1, MAPK-8, EGFR, PRKCB, PTGS-2, and BCL-2. Gene ontology biological process analysis further confirmed multiple viral infection-related processes (P < 0.001), including viral life cycle, modulation by virus, C-C chemokine receptor activity, and platelet activation. KEGG pathway analysis involves multiple pathways (P < 0.05), including FoxO, GnRH, ErbB, Neurotrophin, Toll-like receptor, IL-17, TNF, Insulin, HIF-1, JAK-STAT, Estrogen, NF-kappa, Chemokine, VEGF, and Thyroid hormone signaling pathway in SARS-CoV-2. Docking study was carried out to predict the molecular mechanism Thus, the potential drug combinations could reduce viral infectivity, viral replication, and abnormal host inflammatory responses and may be useful for multi-target drugs against SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Repositioning , SARS-CoV-2/drug effects , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Ascorbic Acid/metabolism , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , COVID-19/virology , Drug Development , Drug Therapy, Combination , Humans , Hydroxychloroquine/metabolism , Hydroxychloroquine/pharmacology , Hydroxychloroquine/therapeutic use , Lopinavir/metabolism , Lopinavir/pharmacology , Lopinavir/therapeutic use , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Binding , Protein Interaction Mapping , Protein Interaction Maps , Ritonavir/metabolism , Ritonavir/pharmacology , Ritonavir/therapeutic use , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Signal Transduction , Virus Replication/drug effects
16.
Nutrients ; 12(11)2020 Oct 27.
Article in English | MEDLINE | ID: covidwho-895391

ABSTRACT

Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19). Research has indicated that patients with pneumonia and sepsis have low vitamin C status and elevated oxidative stress. Administration of vitamin C to patients with pneumonia can decrease the severity and duration of the disease. Critically ill patients with sepsis require intravenous administration of gram amounts of the vitamin to normalize plasma levels, an intervention that some studies suggest reduces mortality. The vitamin has pleiotropic physiological functions, many of which are relevant to COVID-19. These include its antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions. Preliminary observational studies indicate low vitamin C status in critically ill patients with COVID-19. There are currently a number of randomized controlled trials (RCTs) registered globally that are assessing intravenous vitamin C monotherapy in patients with COVID-19. Since hypovitaminosis C and deficiency are common in low-middle-income settings, and many of the risk factors for vitamin C deficiency overlap with COVID-19 risk factors, it is possible that trials carried out in populations with chronic hypovitaminosis C may show greater efficacy. This is particularly relevant for the global research effort since COVID-19 is disproportionately affecting low-middle-income countries and low-income groups globally. One small trial from China has finished early and the findings are currently under peer review. There was significantly decreased mortality in the more severely ill patients who received vitamin C intervention. The upcoming findings from the larger RCTs currently underway will provide more definitive evidence. Optimization of the intervention protocols in future trials, e.g., earlier and sustained administration, is warranted to potentially improve its efficacy. Due to the excellent safety profile, low cost, and potential for rapid upscaling of production, administration of vitamin C to patients with hypovitaminosis C and severe respiratory infections, e.g., COVID-19, appears warranted.


Subject(s)
Ascorbic Acid/therapeutic use , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Vitamins/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Ascorbic Acid/pharmacology , Ascorbic Acid Deficiency/complications , Ascorbic Acid Deficiency/drug therapy , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Critical Illness , Humans , Nutritional Status , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2 , Severe Acute Respiratory Syndrome/drug therapy , Severe Acute Respiratory Syndrome/virology , Vitamins/pharmacology
17.
Pharmacol Rep ; 72(6): 1517-1528, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-893372

ABSTRACT

The mainstay of management of coronavirus disease 2019 (COVID-19) is mainly supportive as to date there is no effective antiviral treatment, apart from remdesivir which has been approved by Food and Drug administration (FDA) for treatment of COVID-19, or vaccine. Supplementation with micronutrients, such as vitamins and minerals, has gained an increasing interest as part of the supportive management of COVID-19. Vitamin C levels in serum and leukocytes are depleted during the acute stage of infection owing to increased metabolic demands. High-dose vitamin C supplement helps to normalise both serum and leukocytes vitamin C levels. Vitamin C has multiple pharmacological characteristics, antiviral, anti-oxidant, anti-inflammatory and immunomodulatory effects, which make it a potential therapeutic option in management of COVID-19. The use of high dose of intravenous vitamin C for management of COVID-19 in China and the United Stated has shown promising results. There were no reported adverse reactions with the short-term use of high dose of vitamin C. Given the fact that vitamin C is cheap, available and safe drug with beneficial effects in management of viral infections and critically ill patients reported in previous clinical trials, it is sensible to add it to COVID-19 management protocol particularly if the current ongoing clinical trials testing the effect of vitamin C in management of COVID-19 show positive results.


Subject(s)
Ascorbic Acid/administration & dosage , COVID-19/drug therapy , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Ascorbic Acid/pharmacology , COVID-19/virology , Dietary Supplements , Dose-Response Relationship, Drug , Humans
18.
Brief Bioinform ; 22(3)2021 05 20.
Article in English | MEDLINE | ID: covidwho-827715

ABSTRACT

Sepsis is a life-threatening complication of pneumonia, including coronavirus disease-2019 (COVID-19)-induced pneumonia. Evidence of the benefits of vitamin C (VC) for the treatment of sepsis is accumulating. However, data revealing the targets and molecular mechanisms of VC action against sepsis are limited. In this report, a bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets, biological functions, and the signaling pathways of VC action against sepsis. As shown in network assays, 63 primary causal targets for the VC action against sepsis were identified from the data, and four optimal core targets for the VC action against sepsis were identified. These core targets were epidermal growth factor receptor (EGFR), mitogen-activated protein kinase-1 (MAPK1), proto-oncogene c (JUN), and signal transducer and activator of transcription-3 (STAT3). In addition, all biological processes (including a top 20) and signaling pathways (including a top 20) potentially involved in the VC action against sepsis were identified. The hub genes potentially involved in the VC action against sepsis and interlaced networks from the Kyoto Encyclopedia of Genes and Genomes Mapper assays were highlighted. Considering all the bioinformatic findings, we conclude that VC antisepsis effects are mechanistically and pharmacologically implicated with suppression of immune dysfunction-related and inflammation-associated functional processes and other signaling pathways. These primary predictive biotargets may potentially be used to treat sepsis in future clinical practice.


Subject(s)
Ascorbic Acid/therapeutic use , COVID-19/complications , Computational Biology , Sepsis/drug therapy , Signal Transduction/drug effects , Ascorbic Acid/pharmacology , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/virology , Gene Expression/drug effects , Humans , Protein Interaction Maps , SARS-CoV-2/isolation & purification , Sepsis/etiology , Sepsis/metabolism
19.
Cell Res ; 31(4): 415-432, 2021 04.
Article in English | MEDLINE | ID: covidwho-759580

ABSTRACT

Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.


Subject(s)
Aging , SARS-CoV-2/physiology , Transcriptome , Alveolar Epithelial Cells/cytology , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/virology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Ascorbic Acid/pharmacology , COVID-19/pathology , COVID-19/virology , Cell Line , Endothelial Cells/cytology , Endothelial Cells/metabolism , Endothelial Cells/virology , Humans , Interleukin-7/metabolism , Interleukin-7/pharmacology , Macaca fascicularis , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/virology , RNA-Seq , SARS-CoV-2/isolation & purification , Single-Cell Analysis , Transcriptome/drug effects
20.
Aging Clin Exp Res ; 32(10): 2115-2131, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-738008

ABSTRACT

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.


Subject(s)
Betacoronavirus/immunology , Betacoronavirus/pathogenicity , Coronavirus Infections/diet therapy , Coronavirus Infections/prevention & control , Cytokines/immunology , Pandemics/prevention & control , Pneumonia, Viral/diet therapy , Pneumonia, Viral/prevention & control , Vitamins/immunology , Vitamins/therapeutic use , Aged , Ascorbic Acid/immunology , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Th17 Cells/drug effects , Th17 Cells/immunology , Vitamin A/immunology , Vitamin A/pharmacology , Vitamin A/therapeutic use , Vitamin D/immunology , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamin E/immunology , Vitamin E/pharmacology , Vitamin E/therapeutic use , Vitamins/pharmacology
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