An Integrated Strategy Designed to Explore the Common and Diverging Mechanisms of Potential Drugs against the Novel Coronavirus Pneumonia Based on Network Pharmacology and in Silico Molecular Docking Technology

Drug repositioning may be a promising way to find potential therapies against coronavirus disease 2019. Although chloroquine and hydroxychloroquine showed controversial results against the coronavirus disease 2019 disease, the potential common and diverging mechanisms of action are not reported and need to be dissected for better understanding them. An integrated strategy was proposed to systematically decipher the common and diverging aspects of mechanism of chloroquine and hydroxychloroquine against coronavirus disease 2019-disease network based on network pharmacology and in silico molecular docking. Potential targets of the two drugs and coronavirus disease 2019 related genes were collected from online public databases. Target function enrichment analysis, tissue enrichment maps and molecular docking analysis were carried out to facilitate the systematic understanding of common and diverging mechanisms of the two drugs. Our results showed that 51 chloroquine targets and 47 hydroxychloroquine targets were associated with coronavirus disease 2019. The core targets include tumor necrosis factor, glyceraldehyde 3-phosphate dehydrogenase, lymphocyte-specific protein-tyrosine kinase, beta-2 microglobulin, nuclear receptor coactivator 1, peroxisome proliferator-activated receptor gamma and glutathione disulfide reductase. Both chloroquine and hydroxychloroquine had good binding affinity towards tumor necrosis factor (affinity=-8.6 and -8.4 kcal/mol, respectively) and glyceraldehyde 3-phosphate dehydrogenase (-7.5 and -7.5 kcal/mol). Chloroquine and hydroxychloroquine both had good affinity with angiotensin-converting enzyme 2, 3-chymotrypsin-like protease and transmembrane serine protease 2. However, hydroxychloroquine manifested better binding affinity with the three proteins comparing with that of chloroquine. Chloroquine and hydroxychloroquine could have potential to inhibit over-activated immunity and inflammation. The potential tissue-specific regulation of the two drugs against severe acute respiratory syndrome coronavirus 2 infection may related with the lung, liver, brain, placenta, kidney, blood, eye, etc. In conclusion, our data systematically demonstrated chloroquine and hydroxychloroquine may have potential regulatory effects on coronavirus disease 2019 disease network, which may affect multiple organs, protein targets and pathways. Routine measurements of the chloroquine and hydroxychloroquine blood concentrations and tailored therapy regimen may be essential. But, further rigorous and high quality randomized controlled clinical trials are warranted to validate the antiviral effects of chloroquine and hydroxychloroquine against severe acute respiratory syndrome coronavirus 2. Our proposed strategy could facilitate the drug repurposing efforts for coronavirus disease 2019 treatment.

FATE OF THE FACE MASKS IN THE ENVIRONMENT AFFECT HUMAN AND WILDLIFE: TONS OF FACE MASKS ARE NEW SOURCE FOR THE ENDOCRINE DISRUPTING CHEMICALS

COVID-19 pandemic has become a major public health problem affecting the lives of billions of people worldwide. There is an effective vaccine treatment for the coronavirus infection, but self-isolation and self-protection are the important options to stop the spread of the virus. Usage of the surgical and other face masks are must during COVID-19 pandemic and millions of used masks are accumulating as trash in the environment every day worldwide. Face masks are made of plastic materials mainly polypropylene which is categorized as endocrine disruptor affecting both humans and wildlife. Contamination of face masks to soil, oceans, sea and air may have increased the amount of microplastics concentration and these microplastics from the face masks may have various negative effects on the environment. However, what needs to be done to protect the environment and public health is to dispose of these masks in a very convenient way. Therefore, accurate elimination and collection of used face masks from the environment should be considered to protect our world. Nowadays there are different types of vaccines are in the protecting against death, hospitalization and seriousness of the COVID-19 infection but using face masks are simple, seems safe and effective way from protection against the disease. In this review, we aimed to draw attention to the fact that a using a face mask is very important for staying safe, but they may cause environmental pollution and have adverse effects on directly health and environment.

Study to estimate levels of oxidative stress biomarkers in long COVID patients

Background: We estimated levels of oxidative stress biomarkers (Lipid peroxidation (LPO) via Malondialdehyde MDA concentration , Superoxide dismutase (SOD), Glutathione Reductase (GR) and Total antioxidant activity (TAA) in patients who were symptomatic beyond 4 weeks of COVID infection. Methods: It's a single centre, hospital based case control study in which levels of oxidative stress biomarkers in 40 Long COVID patients and 40 healthy controls were compared and analysed with their clinico-radiological profile. Results: 1. Lipid peroxidation (MDA) was significantly higher (1155.9 ± 204.82nmole/ml) in Long COVID patients as compared to control (715.5 ± 85.51nmole/ml) (p value 0.0405) 2. SOD in Long COVID patients was lower (18.05 ± 2.83 unit/mg) as compared to control (27.36 ± 2.18 unit/ mg) (p value 0.0096) 3. GR was reduced in Long COVID patients (10.2 ± 1.26 unit/min/mg of protein) as compared to control (15.7 ± 1.42 unit/min/mg of protein) (p value 0.0356) 4. TAA was also moderated in Long COVID patients (94.61 ± 16.40mM) as compared to control (241.64 ± 12.95mM) , (p value 0.0486) 5. LPO was directly and remaining markers were inversely proportional to the Severity of COVID and Xray Severity score 6. The patients with added comorbidities showed even higher oxidative stress than those with no comorbidities (p value 0.05) 7. Lipid peroxidation was significantly high in patients who developed neurological sequelae after COVID infection (p value 0.0083). Conclusion: A subset of patients develop a sequelae to COVID infection and in those patients oxidative stress plays a major role.

Kombucha - An ancient fermented beverage with desired bioactivities: A narrowed review.

Kombucha, originated in China 2000  years ago, is a sour and sweet-tasted drink, prepared traditionally through fermentation of black tea. During the fermentation of kombucha, consisting of mainly acidic compounds, microorganisms, and a tiny amount of alcohol, a biofilm called SCOBY forms. The bacteria in kombucha has been generally identified as Acetobacteraceae. Kombucha is a noteworthy source of B complex vitamins, polyphenols, and organic acids (mainly acetic acid). Nowadays, kombucha is tended to be prepared with some other plant species, which, therefore, lead to variations in its composition. Pre-clinical studies conducted on kombucha revealed that it has desired bioactivities such as antimicrobial, antioxidant, hepatoprotective, anti-hypercholestorelomic, anticancer, anti-inflammatory, etc. Only a few clinical studies have been also reported. In the current review, we aimed to overhaul pre-clinical bioactivities reported on kombucha as well as its brief compositional chemistry. The literature data indicate that kombucha has valuable biological effects on human health.

Profiling serum levels of glutathione reductase and interleukin-10 in positive and negative-PCR COVID-19 outpatients: A comparative study from southwestern Iran.

Since the outbreak of COVID-19 in China, it has rapidly spread across many other countries. We evaluated antioxidant defense systems and inflammatory status related to the SARS-CoV2 infection in a population from southwestern Iran. Comorbidities and clinical symptoms of 104 subjects (comprising negative and positive-PCR COVID-19 outpatients) were assessed. Serum concentrations of glutathione reductase (GR) and interleukin-10 (IL-10) were measured using ELISA. In the positive-PCR group, follow-ups on clinical symptoms were carried out for 28 days at 7-day intervals. In the positive-PCR group, hypertension, diabetes, liver disease, chronic heart disease, and chronic kidney disease were the most common comorbidities. In the general category of symptoms, we found a significant difference between negative and positive-PCR groups, except regarding runny noses. In the pulmonary category, there was a significant difference between the two groups except in terms of chest pain. We also determined a significant difference in neurologic symptoms, except for ear pain, between negative and positive-PCR groups. We also found significantly lower levels of GR but higher levels of IL-10 in the positive-PCR group (p = 0.000 for both). In the positive-PCR group, serum levels of IL-10 (odds ratio = 0.914, p = 0.012) decreased the chances of neurological symptoms occurring over time. The antioxidant defense systems of positive-PCR outpatients failed as demonstrated by a reduction in the serum levels of GR. We also indicated a dysregulation in the immune response against COVID-19, characterized by changes in serum IL-10 levels.

Melatonin restores neutrophil functions and prevents apoptosis amid dysfunctional glutathione redox system.

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.