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1.
Front Cell Infect Microbiol ; 14: 1348713, 2024.
Article En | MEDLINE | ID: mdl-38510969

Sepsis is a potentially fatal condition characterized by organ dysfunction caused by an imbalanced immune response to infection. Although an increased inflammatory response significantly contributes to the pathogenesis of sepsis, several molecular mechanisms underlying the progression of sepsis are associated with increased cellular reactive oxygen species (ROS) generation and exhausted antioxidant pathways. This review article provides a comprehensive overview of the involvement of ROS in the pathophysiology of sepsis and the potential application of antioxidants with antimicrobial properties as an adjunct to primary therapies (fluid and antibiotic therapies) against sepsis. This article delves into the advantages and disadvantages associated with the utilization of antioxidants in the therapeutic approach to sepsis, which has been explored in a variety of animal models and clinical trials. While the application of antioxidants has been suggested as a potential therapy to suppress the immune response in cases where an intensified inflammatory reaction occurs, the use of multiple antioxidant agents can be beneficial as they can act additively or synergistically on different pathways, thereby enhancing the antioxidant defense. Furthermore, the utilization of immunoadjuvant therapy, specifically in septic patients displaying immunosuppressive tendencies, represents a promising advancement in sepsis therapy.


Antioxidants , Sepsis , Animals , Humans , Antioxidants/pharmacology , Antioxidants/therapeutic use , Antioxidants/metabolism , Reactive Oxygen Species/metabolism , Oxidative Stress/physiology , Sepsis/drug therapy , Sepsis/metabolism , Mitochondria/metabolism
2.
PeerJ ; 12: e16793, 2024.
Article En | MEDLINE | ID: mdl-38282857

Background: Water deprivation-induced hypoxia stress (WDIHS) has been extensively investigated in numerous fish species due to their adaptation with accessory respiratory organs to respire air but this has not been studied in Indian stinging fish Heteropneustes fossilis. Data regarding WDIHS-induced metabolism in accessory respiratory organ (ARO) and gills and its relationship with oxidative stress (OS) in respiratory organs of air-breathing fish H. fossilis, are limited. So, this study aimed to investigate the effects of WDIHS (0, 3, 6, 12, and 18 h) on hydrogen peroxide (H2O2) as reactive oxygen species (ROS), OS, redox regulatory enzymes, and electron transport enzymes (ETC) in ARO and gills of H. fossilis. Methods: Fish were exposed to air for different hours (up to 18 h) against an appropriate control, and ARO and gills were sampled. The levels of oxygen saturation in the body of the fish were assessed at various intervals during exposure to air. Protein carbonylation (PC) and thiobarbituric acid reactive substances (TBARS) were used as OS markers, H2O2 as ROS marker, and various enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), along with the assessment of complex enzymes (I, II, III, and V) as well as the levels of ascorbic acid (AA) and the reduced glutathione (GSH) were quantified in both the tissues. Results: Discriminant function analyses indicate a clear separation of the variables as a function of the studied parameters. The gills exhibited higher levels of GSH and H2O2 compared to ARO, while ARO showed elevated levels of PC, TBARS, AA, SOD, CAT, and GPx activities compared to the gills. The activities of GR and ETC enzymes exhibited similar levels in both the respiratory organs, namely the gills, and ARO. These organs experienced OS due to increased H2O2, TBARS, and PC levels, as observed during WDIHS. Under WDIHS conditions, the activity/level of CAT, GPx, GR, and GSH decreased in ARO, while SOD activity, along with GR, GSH, and AA levels decreased in gills. However, the activity/level of SOD and AA in ARO and CAT in gills was elevated under WDIHS. Complex II exhibited a positive correlation with WDIHS, while the other ETC enzymes (complex I, III, and V) activities had negative correlations with the WDIHS. Discussion: The finding suggests that ARO is more susceptible to OS than gills under WDIHS. Despite both organs employ distinct redox regulatory systems to counteract this stress, their effectiveness is hampered by the inadequacy of small redox regulatory molecules and the compromised activity of the ETC, impeding their ability to effectively alleviate the stress induced by the water-deprivation condition.


Catfishes , Water Deprivation , Animals , Reactive Oxygen Species/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Hydrogen Peroxide/metabolism , Oxidative Stress , Superoxide Dismutase/metabolism , Ascorbic Acid/metabolism , Dehydration , Glutathione Peroxidase/metabolism , Hypoxia , Catfishes/metabolism
3.
Front Nutr ; 10: 1275341, 2023.
Article En | MEDLINE | ID: mdl-38099188

Meat is a rich source of high biological proteins, vitamins, and minerals, but it is devoid of dietary fiber, an essential non-digestible carbohydrate component such as cellulose, hemicellulose, pectin, lignin, polysaccharides, and oligosaccharides. Dietary fibers are basically obtained from various cereals, legumes, fruits, vegetables, and their by-products and have numerous nutritional, functional, and health-benefiting properties. So, these fibers can be added to meat products to enhance their physicochemical properties, chemical composition, textural properties, and organoleptic qualities, as well as biological activities in controlling various lifestyle ailments such as obesity, certain cancers, type-II diabetes, cardiovascular diseases, and bowel disorders. These dietary fibers can also be used in meat products as an efficient extender/binder/filler to reduce the cost of production by increasing the cooking yield as well as by reducing the lean meat content and also as a fat replacer to minimize unhealthy fat content in the developed meat products. So, growing interest has been observed among meat processors, researchers, and scientists in exploring various new sources of dietary fibers for developing dietary fiber-enriched meat products in recent years. In the present review, various novel sources of dietary fibers, their physiological effects, their use in meat products, and their impact on various physicochemical, functional, and sensory attributes have been focused.

4.
J Biomol Struct Dyn ; : 1-14, 2023 Dec 27.
Article En | MEDLINE | ID: mdl-38149859

Leukemia is a haematological malignancy affecting blood and bone marrow, ranking 10th among the other common cancers. DNA methylation is an epigenetic dysregulation that plays a critical role in leukemogenesis. DNA methyltransferases (DNMTs) such as DNMT1, DNMT3A and DNMT3B are the key enzymes catalysing DNA methylation. Inhibition of DNMT1 with secondary metabolites from medicinal plants helps reverse DNA methylation. The present study focuses on inhibiting DNMT1 protein (PDB ID: 3PTA) with annonaceous acetogenins through in-silico studies. The docking and molecular dynamic (MD) simulation study was carried out using Schrödinger Maestro and Desmond, respectively. These compounds' drug likeliness, ADMET properties and bioactivity scores were analysed. About 76 different acetogenins were chosen for this study, among which 17 showed the highest binding energy in the range of -8.312 to -10.266 kcal/mol. The compounds with the highest negative binding energy were found to be annohexocin (-10.266 kcal/mol), isoannonacinone (-10.209 kcal/mol) and annonacin (-9.839 kcal/mol). MD simulation results reveal that annonacin remains stable throughout the simulation time of 100 ns and also binds to the catalytic domain of DNMT1 protein. From the above results, it can be concluded that annonacin has the potential to inhibit the DNA methylation process and prevent leukemogenesis.Communicated by Ramaswamy H. Sarma.

5.
Front Endocrinol (Lausanne) ; 14: 1217165, 2023.
Article En | MEDLINE | ID: mdl-37701897

Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD is multifactorial and results from a complex interplay between mucosal immunity, environmental factors, and host genetics. Future therapeutics for GI disorders, including IBD, that are driven by oxidative stress require a greater understanding of the cellular and molecular mechanisms mediated by reactive oxygen species (ROS). In the GI tract, oxidative stressors include infections and pro-inflammatory responses, which boost ROS generation by promoting the production of pro-inflammatory cytokines. Nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) represent two important signaling pathways in intestinal immune cells that regulate numerous physiological processes, including anti-inflammatory and antioxidant activities. Natural antioxidant compounds exhibit ROS scavenging and increase antioxidant defense capacity to inhibit pro-oxidative enzymes, which may be useful in IBD treatment. In this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic compounds including thymol, alkaloids such as berberine, storage polysaccharides such as tamarind xyloglucan, and other phytochemicals represented by isothiocyanate sulforaphane and food/spices (such as ginger, flaxseed oil), as well as antioxidant hormones like melatonin that target cellular signaling pathways to reduce intestinal inflammation occurring with IBD.


Antioxidants , Inflammatory Bowel Diseases , Humans , Antioxidants/therapeutic use , Reactive Oxygen Species , Anthocyanins , Oxidative Stress , Inflammatory Bowel Diseases/drug therapy , Hormones , Inflammation/drug therapy
6.
Front Physiol ; 14: 1217666, 2023.
Article En | MEDLINE | ID: mdl-37435307

Microplastics and pesticides are emerging contaminants in the marine biota, which cause many harmful effects on aquatic organisms, especially on fish. Fish is a staple and affordable food source, rich in animal protein, along with various vitamins, essential amino acids, and minerals. Exposure of fish to microplastics, pesticides, and various nanoparticles generates ROS and induces oxidative stress, inflammation, immunotoxicity, genotoxicity, and DNA damage and alters gut microbiota, thus reducing the growth and quality of fish. Changes in fish behavioral patterns, swimming, and feeding habits were also observed under exposures to the above contaminants. These contaminants also affect the Nrf-2, JNK, ERK, NF-κB, and MAPK signaling pathways. And Nrf2-KEAP1 signalling modulates redox status marinating enzymes in fish. Effects of pesticides, microplastics, and nanoparticles found to modulate many antioxidant enzymes, including superoxide dismutase, catalase, and glutathione system. So, to protect fish health from stress, the contribution of nano-technology or nano-formulations was researched. A decrease in fish nutritional quality and population significantly impacts on the human diet, influencing traditions and economics worldwide. On the other hand, traces of microplastics and pesticides in the habitat water can enter humans by consuming contaminated fish which may result in serious health hazards. This review summarizes the oxidative stress caused due to microplastics, pesticides and nano-particle contamination or exposure in fish habitat water and their impact on human health. As a rescue mechanism, the use of nano-technology in the management of fish health and disease was discussed.

7.
Front Microbiol ; 14: 1194794, 2023.
Article En | MEDLINE | ID: mdl-37448573

The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CLpro). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinski's rule of 5, high binding affinity (highest binding affinity: -9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CLpro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19.

8.
Front Med (Lausanne) ; 10: 1147373, 2023.
Article En | MEDLINE | ID: mdl-37181347

Medical-grade oxygen is the basic need for all medical complications, especially in respiratory-based discomforts. There was a drastic increase in the demand for medical-grade oxygen during the current pandemic. The non-availability of medical-grade oxygen led to several complications, including death. The oxygen concentrator was only the last hope for the patient during COVID-19 pandemic around the globe. The demands also are everlasting during other microbial respiratory infections. The yield of oxygen using conventional molecular zeolites in the traditional oxygen concentrator process is less than the yield noticed when its nano-form is used. Nanotechnology has enlightened hope for the efficient production of oxygen by such oxygen concentrators. Here in the current review work, the authors have highlighted the basic structural features of oxygen concentrators along with the current working principle. Besides, it has been tried to bridge the gap between conventional oxygen concentrators and advanced ones by using nanotechnology. Nanoparticles being usually within 100 nm in size have a high surface area to volume ratio, which makes them suitable adsorbents for oxygen. Here authors have suggested the use of nano zeolite in place of molecular zeolites in the oxygen concentrator for efficient delivery of oxygen by the oxygen concentrators.

9.
Vaccines (Basel) ; 11(2)2023 Feb 17.
Article En | MEDLINE | ID: mdl-36851345

Mycoplasma sp. comprises cell wall-less bacteria with reduced genome size and can infect mammals, reptiles, birds, and plants. Avian mycoplasmosis, particularly in chickens, is primarily caused by Mycoplasma gallisepticum (MG) and Mycoplasma synoviae. It causes infection and pathology mainly in the respiratory, reproductive, and musculoskeletal systems. MG is the most widely distributed pathogenic avian mycoplasma with a wide range of host susceptibility and virulence. MG is transmitted both by horizontal and vertical routes. MG infection induces innate, cellular, mucosal, and adaptive immune responses in the host. Macrophages aid in phagocytosis and clearance, and B and T cells play critical roles in the clearance and prevention of MG. The virulent factors of MG are adhesion proteins, lipoproteins, heat shock proteins, and antigenic variation proteins, all of which play pivotal roles in host cell entry and pathogenesis. Prevention of MG relies on farm and flock biosecurity, management strategies, early diagnosis, use of antimicrobials, and vaccination. This review summarizes the vital pathogenic mechanisms underlying MG infection and recapitulates the virulence factors of MG-host cell adhesion, antigenic variation, nutrient transport, and immune evasion. The review also highlights the limitations of current vaccines and the development of innovative future vaccines against MG.

10.
Environ Geochem Health ; 45(3): 751-770, 2023 Mar.
Article En | MEDLINE | ID: mdl-35306623

Positive effects of COVID-19-induced lockdowns on environment are well documented although pre-planned experiments for such analyses and appearance of fish species are lacking. We hypothesize that spotting the fish Aplocheilus panchax along the industrial belt of Mahanadi River near Cuttack in a never seen manner could be due to the regenerated environment. Heavy metals, water and air qualities along with spotting A. panchax in up, mid and downstream of Mahanadi River near Jagatpur industrial basins were analysed during pre-(end of March 2020) and after 60 days of lockdowns (last week of May 2020). An overall 45, 61, 79, 100, 97 and 90% reduction of Fe, Cu, Ni, Cd, Pb and Zn was recorded in the studied area after lockdowns, respectively. Similarly, dissolved oxygen and pH were elevated by 26 and 7%, respectively. Water temperature, conductivity and total dissolved solute levels were reduced by 7, 46 and 15%, respectively, which were again elevated during post-lockdowns during 2021 as observed from the Landsat-8 OLI satellite data. Air NO2, SO2, NH3, PM2.5, PM10 and CO levels were alleviated by 58.75, 80.33, 72.22, 76.28, 77.33 and 80.15%, respectively. Finally, for the first time, about 12 A. panchax fish per 100 m shore line in the area were spotted. The observed lockdown-induced environmental healing at the studied area could contribute to the appearance of A. panchax in the study site and therefore a stringent environmental audit is suggested during post-COVID-19 periods to make the regenerated environmental status long lasting in such habitats.


Air Pollution , COVID-19 , Cyprinodontiformes , Metals, Heavy , Animals , Environmental Monitoring , COVID-19/epidemiology , Communicable Disease Control , Metals, Heavy/toxicity , Metals, Heavy/analysis , Air Pollution/analysis , India/epidemiology , Water/analysis
11.
Environ Geochem Health ; 45(5): 2591-2610, 2023 May.
Article En | MEDLINE | ID: mdl-36063241

Information on the oxidative stress physiology parameters (OSPP) in general and as a function of the fluctuation of Mg, Ca and organic carbon present in soil and aquatic physico-chemical factors such as pH, temperature and salinity in particular are scanty in the amphibious snail Pila globosa. A spatio-temporal analysis of redox metabolism (as OSPP) followed by discriminant function analysis of the obtained data were performed in P. globosa sampled from the east-coasts of Odisha state, India (mostly along the Bay of Bengal) for environmental health assessment purposes. Results revealed that the OSPP are susceptible to seasonal synergistic variation of soil and physico-chemical factors. Overall, lipid peroxidation, total antioxidant capacity, activities of catalase, glutathione reductase had positive correlation whereas ascorbic acid, the reduced glutathione and the activity of superoxide dismutase had non-significant correlation with the soil Mg, Ca, organic carbon, and pH, temperature and salinity of water. In the summer season, the snails had a marked 51.83% and 26.41% higher lipid peroxidation level and total antioxidative activity as compared to the other seasons. Spatial variation of OSPP indicates that snails residing away from the Bay of Bengal coast had at least 4.4% lower antioxidant level in winter and 30% higher lipid peroxide levels in summer as compared to the rest of the sampling sites. Results on OSPP in P. globosa may be useful for monitoring the ecotoxic effects of environment using molluscs in general and P. globosa in particular.


Antioxidants , Carbon , Animals , Antioxidants/metabolism , Carbon/metabolism , Oxidative Stress , Snails/metabolism , Ascorbic Acid/metabolism
12.
Front Endocrinol (Lausanne) ; 13: 1027237, 2022.
Article En | MEDLINE | ID: mdl-36440220

Type 2 diabetes mellitus is a metabolic disorder resulting from impaired insulin secretion and resistance. Dipeptidyl peptidase (DPP)-IV is an enzyme known to trigger the catalysis of insulinotropic hormones, further abating the endogenous insulin levels and elevating the glucose levels in blood plasma. In the field of drug development, DPP-IV inhibitors have opened up numerous opportunities for leveraging this target to generate compounds as hypoglycemic agents by regulating incretin activity and subsequently decreasing blood glucose levels. However, the practice of synthetic drugs is an apparent choice but poses a great pharmacovigilance issue due to their incessant undesirable effects. The ideology was set to inventively look upon different ethnomedicinal plants for their anti-diabetic properties to address these issues. To date, myriads of phytochemicals are characterized, eliciting an anti-diabetic response by targeting various enzymes and augmenting glucose homeostasis. Antioxidants have played a crucial role in alleviating the symptoms of diabetes by scavenging free radicals or treating the underlying causes of metabolic disorders and reducing free radical formation. Plant-based DPP-IV inhibitors, including alkaloids, phenolic acid, flavonoids, quercetin, and coumarin, also possess antioxidant capabilities, providing anti-diabetic and antioxidative protection. This review article provides a new gateway for exploring the ability of plant-based DPP-IV inhibitors to withstand oxidative stress under pathological conditions related to diabetes and for reforming the strategic role of ethnomedicinal plants as potent DPP-IV inhibitors through the development of polyherbal formulations and nanophytomedicines to regulate incretin activity.


Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Humans , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Incretins/metabolism , Incretins/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Glucose
13.
Cancers (Basel) ; 14(18)2022 Sep 19.
Article En | MEDLINE | ID: mdl-36139697

The ongoing rise in the number of cancer cases raises concerns regarding the efficacy of the various treatment methods that are currently available. Consequently, patients are looking for alternatives to traditional cancer treatments such as surgery, chemotherapy, and radiotherapy as a replacement. Medicinal plants are universally acknowledged as the cornerstone of preventative medicine and therapeutic practices. Annona muricata is a member of the family Annonaceae and is familiar for its medicinal properties. A. muricata has been identified to have promising compounds that could potentially be utilized for the treatment of cancer. The most prevalent phytochemical components identified and isolated from this plant are alkaloids, phenols, and acetogenins. This review focuses on the role of A. muricata extract against various types of cancer, modulation of cellular proliferation and necrosis, and bioactive metabolites responsible for various pharmacological activities along with their ethnomedicinal uses. Additionally, this review highlights the molecular mechanism of the role of A. muricata extract in downregulating anti-apoptotic and several genes involved in the pro-cancer metabolic pathways and decreasing the expression of proteins involved in cell invasion and metastasis while upregulating proapoptotic genes and genes involved in the destruction of cancer cells. Therefore, the active phytochemicals identified in A. muricata have the potential to be employed as a promising anti-cancer agent.

14.
Sens Int ; 3: 100180, 2022.
Article En | MEDLINE | ID: mdl-35601184

A major threat that has surrounded human civilization since the beginning of the year 2020 is the outbreak of coronavirus disease 2019 (COVID-19). It has been declared a pandemic by the World Health Organization and significantly affected populations globally, causing medical and economic despair. Healthcare chains across the globe have been under grave stress owing to shortages of medical equipments necessary to address a pandemic. Furthermore, personal protective equipment supplies, mandatory for healthcare staff for treating severely ill patients, have been in short supply. To address the necessary requisites during the pandemic, several researchers, hospitals, and industries collaborated to meet the demand for these medical equipments in an economically viable manner. In this context, 3D printing technologies have provided enormous potential in creating personalized healthcare equipment, including face masks, face shields, rapid detection kits, testing swabs, biosensors, and various ventilator components. This has been made possible by capitalizing on centralized large-scale manufacturing using 3D printing and local distribution of verified and tested computer-aided design files. The primary focus of this study is, "How 3D printing is helpful in developing these equipments, and how it can be helpful in the development and deployment of various sensing and point-of-care-testing (POCTs) devices for the commercialization?" Further, the present study also takes care of patient safety by implementing novel 3D printed health equipment used for COVID-19 patients. Moreover, the study helps identify and highlight the efforts made by various organizations toward the usage of 3D printing technologies, which are helpful in combating the ongoing pandemic.

15.
Article En | MEDLINE | ID: mdl-35182719

In the present study, Water Deprived Condition (WPC, up to 18 h) induced hypoxia and altered oxidative stress (OS) physiology along with responses of respiratory chain enzyme in Heteropneustes fossilis are described . The body O2 saturation level in the fish was declined with respect to air exposure. Higher levels of lipid peroxidation and protein carbonylation were recorded in the tissue of fish exposed to 6 h of WPC stress. The regulation of the mitochondrial complex and antioxidant enzymes, small antioxidant molecules indicated that the fish can moderately survive up to 6 h of air exposure. Probably with the onset of metabolic depression, it can critically resist the dehydration stress up to 18 h. Although the activities of glutathione peroxidase and reductase were elevated, activities of antioxidant enzymes such as superoxide dismutase and catalase were insufficient to combat WPC induced ROS and OS generated under hypoxia. The small antioxidant molecules played a key role in elimination of ROS. The elevated complex II activity was probably responsible for resisting the complex I, II and IV mediated electron leakage events in mitochondria of the fish under WPC. The total H2O2 removing capacity was less under WPC while the total units of all calculated antioxidants were alleviated signifying an interesting mechanism of WPC induced OS in the fish.


Catfishes , Animals , Antioxidants/metabolism , Catalase/metabolism , Catfishes/metabolism , Dehydration/metabolism , Hydrogen Peroxide/metabolism , Hypoxia/metabolism , Lipid Peroxidation , Liver/metabolism , Mitochondria/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism
16.
Front Biosci (Landmark Ed) ; 27(1): 10, 2022 01 11.
Article En | MEDLINE | ID: mdl-35090315

BACKGROUND: Coronavirus disease-2019 (COVID-19) has become a pandemic around the globe due to the Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2), a new variant of the Coronavirus (CoV) family. The rapid transmission of the infectious disease, 135,646,617 positive cases from which 2,930,732 mortality cases were recorded until 11 April 2021. In an emergency, several existing anti-viral, anti-malarial, and anti-HIV drugs have been used on a repurposing basis. However, without proper clinical evidence, it may create several side effects for the patient. Thus, recommending potential and less-toxic regimens at this emergency stage is the most crucial aspect for any physician. METHODS: We have hypothesized a combinatorial drug approach against COVID-19 and to select potential combinations from ten anti-HIV drugs and ten vitamin C derivatives were systematically validated using advanced bioinformatic tools. Initially, the chemical structures used as ligands from PubChem and the target protein, SARS-CoV-2 main protease (PDB ID: 6Y84) from the protein data bank were retrieved for this study. Further, assess the potency, toxicity, drug-ability, and pharmacokinetics profiles using several bioinformatics tools, viz., molecular docking by the AutoDock 4.1 software with predicting activity spectra for substances, Molsoft, ProTox, and SwissADME tools. Molecular dynamics simulation was also employed for most potential candidates to assess their binding stability using GROMACS 5.1.4 software. RESULTS: The above computational investigation indicated that 'darunavir with L-ascorbyl-2,6-dibutyrate or ascorbic acid-2-sulfate' combinations strongly inhibit the SARS-CoV-2-main protease as a potential treatment option against COVID-19. Mostly, vitamin C derivatives enhanced the anti-COVID activity and might reduce the post-treatment side effects of darunavir in combination. CONCLUSIONS: Overall, the present work suggests that bioinformatics tools are suitable for recognizing potential candidates in an emergency, and herein the selected 'anti-HIV-drug-vitamin c derivatives' cocktails may potential-cum-fewer toxic regimens against COVID-19 treatment.


Anti-HIV Agents , COVID-19 Drug Treatment , Ascorbic Acid , Darunavir , Humans , Molecular Docking Simulation , SARS-CoV-2
17.
J Biomol Struct Dyn ; 40(22): 12316-12335, 2022.
Article En | MEDLINE | ID: mdl-34463220

A positive association between oxidative stress and hyper-thyroid conditions is well established. Vitamin E (VIT-E) and curcumin (CRM) are considered as potent antioxidant small molecules. Nuclear factor erythroid 2-related factor 2(NRF-2) is known to bind with antioxidant response element and subsequently activate expression of antioxidant enzymes. However, the activation of NRF-2 depends on removal of its regulator Kelch-like ECH-associated protein 1(NRF-2). In the current study, an attempt is made to demonstrate whether effects of VIT-E and CRM are due to direct interaction with the target proteins (i.e. NRF-2, NRF-2, SOD, catalase and LDH) or by possible interaction with the flanking region of their promoters by in silico analysis. Further, these results were corroborated by pretreatment of H9C2 cells (1 x 106 cells per mL of media) with VIT-E (50 µM) and/or CRM (20 µM) for 24 h followed by induction of oxidative stress via T4 (100 nm) administration and assaying the active oxygen metabolism. Discriminant function analyses (DFA) indicated that T4 has a definite role in increasing oxidative stress as evidenced by induction of ROS generation, increase in mitochondrial membrane potential and elevated lipid peroxidation (LPx). Pretreatment with the two antioxidants have ameliorative effects more so when given in combination. The decline in biological activities of the principal antioxidant enzymes SOD and CAT with respect to T4 treatment and its restoration in antioxidant pretreated group further validated our in silico data. Communicated by Ramaswamy H. Sarma.


Curcumin , Vitamin E , Vitamin E/pharmacology , Antioxidants/pharmacology , Curcumin/pharmacology , Curcumin/metabolism , Molecular Docking Simulation , Oxidative Stress , Oxidation-Reduction , Superoxide Dismutase/genetics , Genes, Regulator , Cell Line , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism
18.
Environ Sci Pollut Res Int ; 29(57): 85595-85611, 2022 Dec.
Article En | MEDLINE | ID: mdl-34390474

Specific areas in many countries such as Italy, India, China, Brazil, Germany and the USA have witnessed that air pollution increases the risk of COVID-19 severity as particulate matters transmit the virus SARS-CoV-2 and causes high expression of ACE2, the receptor for spike protein of the virus, especially under exposure to NO2, SO2 and NOx emissions. Wastewater-based epidemiology of COVID-19 is also noticed in many countries such as the Netherlands, the USA, Paris, France, Australia, Spain, Italy, Switzerland China, India and Hungary. Soil is also found to be contaminated by the RNA of SARS-CoV-2. Activities including defecation and urination by infected people contribute to the source for soil contamination, while release of wastewater containing cough, urine and stool of infected people from hospitals and home isolation contributes to the source of SARS-CoV-2 RNA in both water and soil. Detection of the virus early before the outbreak of the disease supports this fact. Based on this information, spike in pollution is found to be more dangerous in long-term than the spike protein of SARS-CoV-2. It is because the later one may be controlled in future within months or few years by vaccination and with specific drugs, but the former one provides base for many diseases including the current and any future pandemics. Although such predictions and the positive effects of SARS-CoV-2 on environment was already forecasted after the first wave of COVID-19, the learnt lesson as spotlight was not considered as one of the measures for which 2nd wave has quickly hit the world.


COVID-19 , Humans , COVID-19/epidemiology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , RNA, Viral , Soil
19.
Pathogens ; 10(8)2021 Aug 10.
Article En | MEDLINE | ID: mdl-34451472

Wastewater-based epidemiology (WBE) has a long history of identifying a variety of viruses from poliovirus to coronaviruses, including novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The presence and detection of SARS-CoV-2 in human feces and its passage into the water bodies are significant public health challenges. Hence, the hot issue of WBE of SARS-CoV-2 in the coronavirus respiratory disease (COVID-19) pandemic is a matter of utmost importance (e.g., SARS-CoV-1). The present review discusses the background, state of the art, actual status, and prospects of WBE, as well as the detection and quantification protocols of SARS-CoV-2 in wastewater. The SARS-CoV-2 detection studies have been performed in different water matrixes such as influent and effluent of wastewater treatment plants, suburban pumping stations, hospital wastewater, and sewer networks around the globe except for Antarctica. The findings revealed that all WBE studies were in accordance with clinical and epidemiological data, which correlates the presence of SARS-CoV-2 ribonucleic acid (RNA) with the number of new daily positive cases officially reported. This last was confirmed via Reverse Transcriptase-quantitative Polymerase Chain Reaction (RT-qPCR) testing which unfortunately is not suitable for real-time surveillance. In addition, WBE concept may act as a faster protocol to alert the public health authorities to take administrative orders (possible re-emerging infections) due to the impracticality of testing all citizens in a short time with limited diagnostic facilities. A comprehensive and integrated review covering all steps starting from sampling to molecular detection of SARS-CoV-2 in wastewater has been made to guide for the development well-defined and reliable protocols.

20.
Front Biosci (Schol Ed) ; 13(1): 30-43, 2021 06 30.
Article En | MEDLINE | ID: mdl-34256528

Molecular network-based studies have gained tremendous importance in biomedical research. Several such advanced technologies in molecular biology have evolved in the past decade and have contributed to building up enormous molecular data. These molecular networks gained much significance among researchers triggering widespread use of experimental and computational tools. This interest led researchers to compile data of biomolecules systematically and to develop various computational tools for analyzing data. In the present scenario, an enormous amount of molecular network databases are available which can be accessed freely by the public. This is the central focus of this article.


Drug Discovery , Biomedical Research , Computational Biology , Humans
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