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1.
Beverages ; 8(1):13, 2022.
Article in English | ProQuest Central | ID: covidwho-1760334

ABSTRACT

(1) Background: beverages based on extracts from Camellia sinensis are popular worldwide. Due to an increasing number of processed teas on the market, there is a need to develop unified classification standards based on chemical analysis. Meanwhile, phytochemical characterizations are mainly performed on tea samples from China (~80%). Hence, data on teas of other provenances is recommended. (2) Methods: in the present investigation, we characterized lyophilised extracts obtained by infusion, maceration and methanolic extraction derived from tea samples from China, Japan, Sri Lanka and Portugal by phytochemistry (catechins, oxyaromatic acids, flavonols, alkaloids and theanine). The real benefits of drinking the tea were analysed based on the bioavailability of the determined phytochemicals. (3) Results: the infusions revealed the highest total phenolic contents (TPC) amounts, while methanolic extracts yielded the lowest. The correlation matrix indicated that the levels of phenolic compounds were similar in the infusions and methanolic samples, while extractions made by maceration were significantly different. The differences could be partially explained by the different amounts of (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG) and gallic acids (GA). The catechin percentages were significantly lower in the macerations, especially the quantity of EGCG decreases by 4- to 5-fold after this process. (4) Conclusions: the results highlight the importance of the processing methodology to obtain “instant tea”;the composition of the extracts obtained with the same methodology is not significantly affected by the provenance of the tea. However, attention should be drawn to the specificities of the Japanese samples (the tea analysed in the present work was of Sencha quality). In contrast, the extraction methodology significantly affects the phytochemical composition, especially concerning the content of polyphenols. As such, our results indicate that instant tea classification based on chemical composition is sensible, but there is a need for a standard extraction methodology, namely concerning the temperature and time of contact of the tea leaves with the extraction solvent.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329869

ABSTRACT

Background: Since the first case of COVID-19 in Sudan was reported in March 2020, the Federal Ministry of Health adopted an active surveillance system to collect and analyze information from the isolation centers and public and private laboratories about all suspected and confirmed COVID-19 cases. This study used the surveillance data to better understand the distribution and determinants of COVID-19 in Sudan and to construct a threshold level beyond which the dramatic surge may occur. Methods Data of suspected and confirmed COVID-19 cases were extracted from the line list prepared by the Surveillance and Information Department at the Federal Ministry of Health after obtaining ethical approval from the National Ethics Committee. Data were cleaned, coded, and analyzed using SPSS version 21. Frequencies and proportions were used to describe data. A univariate logistic regression analysis was used to determine the association of variables with the positivity of COVID-19. Variables with p -values < 0.05 in the univariate logistic analyses were included in multivariable logistic regression to determine the adjusted odds ratios (ORs) and their 95% confidence interval (CI). A two-sided α of less than 0.05 ( p  < 0.05) was considered statistically significant. Results Out of 48,545 suspected cases, 27,453 were positive. Four waves were seen, with a distinct explosion point of around 200 cases observed nationwide. Khartoum reported the highest number of cases. Of those tested positive, 16,444 (59.9%) were male and 11,009 (40.1%) were female. The mean (SD) age of cases was 41.1 (19.0) years with 21.6% of cases above 60 years. 14,780 (53.8%) of cases were asymptomatic. Fever, cough, shortness of breath, and loss of smell and taste were reported in 32.7%, 26.4%, 19.1 and 4.5% of confirmed cases, respectively. A total of 1,793 confirmed cases died;the case fatality rate was 6.5%. A considerable proportion of infection was reported among health workers. A univariate logistic regression analysis revealed that being symptomatic is significantly associated with testing negative for COVID-19 (odds ratio < 1). Conclusions COVID-19 was widely spread in Sudan with more cases in Khartoum, the capital of Sudan. The country experienced four waves with an observable epidemic explosion point of around 200 positive cases per week nationwide. Around half of the patients were asymptomatic;however, fever, cough, and shortness of breath were the commonest symptoms. The CFR all through was 6.5%, with death having a strong association with age. Further studies are recommended to clarify the image, especially among health workers. The study also highlighted the need to improve the quality of surveillance data.

3.
Pharmaceuticals (Basel) ; 15(3)2022 Mar 03.
Article in English | MEDLINE | ID: covidwho-1732153

ABSTRACT

The main protease (Mpro or 3CLpro) in coronaviruses represents a promising specific drug target as it is essential for the cleavage of the virus polypeptide and has a unique cleavage site that does not exist in human host proteases. In this study, we explored potential natural pan-coronavirus drugs using in vitro and in silico approaches and three coronavirus main proteases as treatment targets. The PyRx program was used to screen 39,442 natural-product-like compounds from the ZINC database and 121 preselected phytochemicals from medicinal plants with known antiviral activity. After assessment with Lipinski's rule of five, molecular docking was performed for the top 33 compounds of both libraries. Enzymatic assays were applied for the top candidates from both in silico approaches to test their ability to inhibit SARS-CoV-2 Mpro. The four compounds (hypericin, rosmarinic acid, isorhamnetin, and luteolin) that most efficiently inhibited SARS-CoV-2 Mpro in vitro were further tested for their efficacy in inhibiting Mpro of SARS-CoV-1 and MERS-CoV. Microscale thermophoresis was performed to determine dissociation constant (Kd) values to validate the binding of these active compounds to recombinant Mpro proteins of SARS-CoV-2, SARS-CoV-1, and MERS-CoV. The cytotoxicity of hypericin, rosmarinic acid, isorhamnetin, and luteolin was assessed in human diploid MRC-5 lung fibroblasts using the resazurin cell viability assay to determine their therapeutic indices. Sequence alignment of Mpro of SARS-CoV-2 demonstrated 96.08%, 50.83%, 49.17%, 48.51%, 44.04%, and 41.06% similarity to Mpro of other human-pathogenic coronaviruses (SARS-CoV-1, MERS-CoV, HCoV-NL63, HCoV-OC43, HCoV-HKU1, and HCoV-229E, respectively). Molecular docking showed that 12 out of 121 compounds were bound to SARS-CoV-2 Mpro at the same binding site as the control inhibitor, GC376. Enzyme inhibition assays revealed that hypericin, rosmarinic acid, isorhamnetin, and luteolin inhibited Mpro of SARS-CoV-2, while hypericin and isorhamnetin inhibited Mpro of SARS-CoV-1; hypericin showed inhibitory effects toward Mpro of MERS-CoV. Microscale thermophoresis confirmed the binding of these compounds to Mpro with high affinity. Resazurin assays showed that rosmarinic acid and luteolin were not cytotoxic toward MRC-5 cells, whereas hypericin and isorhamnetin were slightly cytotoxic. We demonstrated that hypericin represents a potential novel pan-anti-coronaviral agent by binding to and inhibiting Mpro of several human-pathogenic coronaviruses. Moreover, isorhamnetin showed inhibitory effects toward SARS-CoV-2 and SARS-CoV-1 Mpro, indicating that this compound may have some pan-coronaviral potential. Luteolin had inhibitory effects against SARS-CoV-2 Mpro.

4.
Pharmacopsychiatry ; 54(5):215-223, 2021.
Article in English | APA PsycInfo | ID: covidwho-1624294

ABSTRACT

Introduction: Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods. Methods: WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6. Results: WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5. Limitations: Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings. Conclusion: WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

5.
Phytomedicine ; 98: 153930, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1596231

ABSTRACT

BACKGROUND: The worldwide corona virus disease outbreak, generally known as COVID-19 pandemic outbreak resulted in a major health crisis globally. The morbidity and transmission modality of COVID-19 appear more severe and uncontrollable. The respiratory failure and following cardiovascular complications are the main pathophysiology of this deadly disease. Several therapeutic strategies are put forward for the development of safe and effective treatment against SARS-CoV-2 virus from the pharmacological view point but till date there are no specific treatment regimen developed for this viral infection. PURPOSE: The present review emphasizes the role of herbs and herbs-derived secondary metabolites in inhibiting SARS-CoV-2 virus and also for the management of post-COVID-19 related complications. This approach will foster and ensure the safeguards of using medicinal plant resources to support the healthcare system. Plant-derived phytochemicals have already been reported to prevent the viral infection and to overcome the post-COVID complications like parkinsonism, kidney and heart failure, liver and lungs injury and mental problems. In this review, we explored mechanistic approaches of herbal medicines and their phytocomponenets as antiviral and post-COVID complications by modulating the immunological and inflammatory states. STUDY DESIGN: Studies related to diagnosis and treatment guidelines issued for COVID-19 by different traditional system of medicine were included. The information was gathered from pharmacological or non-pharmacological interventions approaches. The gathered information sorted based on therapeutic application of herbs and their components against SARSCoV-2 and COVID-19 related complications. METHODS: A systemic search of published literature was conducted from 2003 to 2021 using different literature database like Google Scholar, PubMed, Science Direct, Scopus and Web of Science to emphasize relevant articles on medicinal plants against SARS-CoV-2 viral infection and Post-COVID related complications. RESULTS: Collected published literature from 2003 onwards yielded with total 625 articles, from more than 18 countries. Among these 625 articles, more than 95 medicinal plants and 25 active phytomolecules belong to 48 plant families. Reports on the therapeutic activity of the medicinal plants belong to the Lamiaceae family (11 reports), which was found to be maximum reported from 4 different countries including India, China, Australia, and Morocco. Other reports on the medicinal plant of Asteraceae (7 reports), Fabaceae (8 reports), Piperaceae (3 reports), Zingiberaceae (3 reports), Ranunculaceae (3 reports), Meliaceae (4 reports) were found, which can be explored for the development of safe and efficacious products targeting COVID-19. CONCLUSION: Keeping in mind that the natural alternatives are in the priority for the management and prevention of the COVID-19, the present review may help to develop an alternative approach for the management of COVID-19 viral infection and post-COVID complications from a mechanistic point of view.

6.
Mar Drugs ; 19(7)2021 Jul 13.
Article in English | MEDLINE | ID: covidwho-1314693

ABSTRACT

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolites from the genus were screened using molecular docking calculations. Promising diterpenes were further characterized by molecular dynamics (MD) simulations based on molecular mechanics-generalized Born surface area (MM-GBSA) binding energy calculations. According to in silico calculations, five cembranoid diterpenes manifested adequate binding affinities as Mpro inhibitors with ΔGbinding < -33.0 kcal/mol. Binding energy and structural analyses of the most potent Sarcophyton inhibitor, bislatumlide A (340), was compared to darunavir, an HIV protease inhibitor that has been recently subjected to clinical-trial as an anti-COVID-19 drug. In silico analysis indicates that 340 has a higher binding affinity against Mpro than darunavir with ΔGbinding values of -43.8 and -34.8 kcal/mol, respectively throughout 100 ns MD simulations. Drug-likeness calculations revealed robust bioavailability and protein-protein interactions were identified for 340; biochemical signaling genes included ACE, MAPK14 and ESR1 as identified based on a STRING database. Pathway enrichment analysis combined with reactome mining revealed that 340 has the capability to re-modulate the p38 MAPK pathway hijacked by SARS-CoV-2 and antagonize injurious effects. These findings justify further in vivo and in vitro testing of 340 as an antiviral agent against SARS-CoV-2.


Subject(s)
Anthozoa/chemistry , COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/pharmacology , Diterpenes/pharmacology , SARS-CoV-2/drug effects , Animals , COVID-19/virology , Coronavirus 3C Proteases/metabolism , Coronavirus Protease Inhibitors/chemistry , Coronavirus Protease Inhibitors/isolation & purification , Diterpenes/chemistry , Diterpenes/isolation & purification , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , SARS-CoV-2/enzymology , SARS-CoV-2/pathogenicity , Structure-Activity Relationship
7.
Pharmacopsychiatry ; 54(5): 215-223, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1217715

ABSTRACT

INTRODUCTION: Depression is responsible for 800 000 deaths worldwide, a number that will rise significantly due to the COVID-19 pandemic. Affordable novel drugs with less severe side effects are urgently required. We investigated the effect of withanone (WN) from Withania somnifera on the serotonin system of wild-type and knockout Caenorhabditis elegans strains using in silico, in vitro, and in vivo methods. METHODS: WN or fluoxetine (as positive control drug) was administered to wild-type (N2) and knockout C. elegans strains (AQ866, DA1814, DA2100, DA2109, and MT9772) to determine their effect on oxidative stress (Trolox, H2DCFDA, and juglone assays) on osmotic stress and heat stress and lifespan. Quantitative real-time RT-PCR was applied to investigate the effect of WN or fluoxetine on the expression of serotonin receptors (ser-1, ser-4, ser-7) and serotonin transporter (mod-5). The binding affinity of WN to serotonin receptors and transporter was analyzed in silico using AutoDock 4.2.6. RESULTS: WN scavenged ROS in wild-type and knockout C. elegans and prolonged their lifespan. WN upregulated the expression of serotonin receptor and transporter genes. In silico analyses revealed high binding affinities of WN to Ser-1, Ser-4, Ser-7, and Mod-5. LIMITATIONS: Further studies are needed to prove whether the results from C. elegans are transferrable to mammals and human beings. CONCLUSION: WN ameliorated depressive-associated stress symptoms by activating the serotonin system. WN may serve as potential candidate in developing new drugs to treat depression.


Subject(s)
Depression , Receptors, Serotonin/metabolism , Serotonin Plasma Membrane Transport Proteins/metabolism , Synaptic Transmission/drug effects , Withanolides/pharmacology , Animals , Animals, Genetically Modified , Antidepressive Agents/pharmacology , COVID-19/psychology , Caenorhabditis elegans , Depression/drug therapy , Depression/metabolism , Fluoxetine/pharmacology , Humans , Longevity/drug effects , Oxidative Stress/drug effects , SARS-CoV-2
8.
Comput Biol Med ; 133: 104362, 2021 06.
Article in English | MEDLINE | ID: covidwho-1188438

ABSTRACT

BACKGROUND: COVID-19, declared a pandemic in March 2020 by the World Health Organization is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The virus has already killed more than 2.3 million people worldwide. OBJECT: The principal intent of this work was to investigate lead compounds by screening natural product library (NPASS) for possible treatment of COVID-19. METHODS: Pharmacophore features were used to screen a large database to get a small dataset for structure-based virtual screening of natural product compounds. In the structure-based screening, molecular docking was performed to find a potent inhibitor molecule against the main protease (Mpro) of SARS-CoV-2 (PDB ID: 6Y7M). The predicted lead compound was further subjected to Molecular Dynamics (MD) simulation to check the stability of the leads compound with the evolution of time. RESULTS: In pharmacophore-based virtual screening, 2,361 compounds were retained out of 30,927. In the structure-based screening, the lead compounds were filtered based on their docking scores. Among the 2,360 compounds, 12 lead compounds were selected based on their docking score. Kazinol T with NPASS ID: NPC474104 showed the highest docking score of -14.355 and passed criteria of Lipinski's drug-like parameters. Monitoring ADMET properties, Kazinol T showed its safety for consumption. Docking of Kazinol T with two Asian mutants (R60C and I152V) showed variations in binding and energy parameters. Normal mode analysis for ligand-bound and unbound form of protease along with its mutants, revealed displacement and correlation parameters for C-alpha atoms. MD simulation results showed that all ligand-protein complexes remained intact and stable in a dynamic environment with negative Gibbs free energy. CONCLUSIONS: The natural product Kazinol T was a predicted lead compound against the main protease of SARS-CoV-2 and will be the possible treatment for COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Peptide Hydrolases , Phytochemicals , Protease Inhibitors/pharmacology
9.
Molecules ; 26(7)2021 Apr 05.
Article in English | MEDLINE | ID: covidwho-1167672

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (Mpro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as Mpro inhibitors with ΔGbinding ≤ -40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 Mpro than lopinavir over 100 ns with ΔGbinding values of -51.9 vs. -33.6 kcal/mol, respectively. Protein-protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target-function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing.


Subject(s)
Invertebrates/chemistry , SARS-CoV-2/metabolism , Terpenes/chemistry , Viral Matrix Proteins/antagonists & inhibitors , Animals , Binding Sites , COVID-19/drug therapy , COVID-19/virology , Humans , Hydrogen Bonding , Invertebrates/metabolism , Lopinavir/chemistry , Lopinavir/metabolism , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/chemistry , Protease Inhibitors/isolation & purification , Protease Inhibitors/therapeutic use , Protein Binding , SARS-CoV-2/isolation & purification , Terpenes/isolation & purification , Terpenes/metabolism , Terpenes/therapeutic use , Thermodynamics , Viral Matrix Proteins/metabolism
10.
Molecules ; 26(7)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1167670

ABSTRACT

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.


Subject(s)
Antidepressive Agents/pharmacology , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Aging/drug effects , Aging/physiology , Animals , Antioxidants/pharmacology , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Gene Knockout Techniques , Heat-Shock Response/drug effects , Longevity/drug effects , Longevity/genetics , Longevity/physiology , Mutation , Osmotic Pressure/drug effects , Oxidative Stress/drug effects , Plant Extracts/chemistry , Reactive Oxygen Species/metabolism
11.
Comput Biol Med ; 133: 104359, 2021 06.
Article in English | MEDLINE | ID: covidwho-1157213

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a major threat worldwide due to its fast spreading. As yet, there are no established drugs available. Speeding up drug discovery is urgently required. We applied a workflow of combined in silico methods (virtual drug screening, molecular docking and supervised machine learning algorithms) to identify novel drug candidates against COVID-19. We constructed chemical libraries consisting of FDA-approved drugs for drug repositioning and of natural compound datasets from literature mining and the ZINC database to select compounds interacting with SARS-CoV-2 target proteins (spike protein, nucleocapsid protein, and 2'-o-ribose methyltransferase). Supported by the supercomputer MOGON, candidate compounds were predicted as presumable SARS-CoV-2 inhibitors. Interestingly, several approved drugs against hepatitis C virus (HCV), another enveloped (-) ssRNA virus (paritaprevir, simeprevir and velpatasvir) as well as drugs against transmissible diseases, against cancer, or other diseases were identified as candidates against SARS-CoV-2. This result is supported by reports that anti-HCV compounds are also active against Middle East Respiratory Virus Syndrome (MERS) coronavirus. The candidate compounds identified by us may help to speed up the drug development against SARS-CoV-2.


Subject(s)
COVID-19 , SARS Virus , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , SARS-CoV-2 , Supervised Machine Learning
12.
Phytomedicine ; 84: 153482, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1051912

ABSTRACT

INTRODUCTION: Approximately 300 million people worldwide suffer from depression. The COVID-19 crisis may dramatically increase these numbers. Severe side effects and resistance development limit the use of standard antidepressants. The steroidal lactone withanolide A (WA) from Withania somnifera may be a promising alternative. Caenorhabditis elegans was used as model to explore WA's anti-depressive and anti-stress potential. METHODS: C. elegans wildtype (N2) and deficient strains (AQ866, DA1814, DA2100, DA2109 and MT9772) were used to assess oxidative, osmotic or heat stress as measured by generation of reactive oxygen species (ROS), determination of lifespan, and mRNA expression of serotonin receptor (ser-1, ser-4, ser-7) and serotonin transporter genes (mod-5). The protective effect of WA was compared to fluoxetine as clinically established antidepressant. Additionally, WA's effect on lifespan was determined. Furthermore, the binding affinities and pKi values of WA, fluoxetine and serotonin as natural ligand to Ser-1, Ser-4, Ser-7, Mod-5 and their human orthologues proteins were calculated by molecular docking. RESULTS: Baseline oxidative stress was higher in deficient than wildtype worms. WA and fluoxetine reduced ROS levels in all strains except MT9772. WA and fluoxetine prolonged survival times in wildtype and mutants under osmotic stress. WA but not fluoxetine increased lifespan of all heat-stressed C. elegans strains except DA2100. Furthermore, WA but not fluoxetine extended lifespan in all non-stressed C. elegans strains. WA also induced mRNA expression of serotonin receptors and transporters in wildtype and mutants. WA bound with higher affinity and lower pKi values to all C. elegans and human serotonin receptors and transporters than serotonin, indicating that WA may competitively displaced serotonin from the binding pockets of these proteins. CONCLUSION: WA reduced stress and increased lifespan by ROS scavenging and interference with the serotonin system. Hence, WA may serve as promising candidate to treat depression.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/drug effects , Longevity/drug effects , Receptors, Serotonin/genetics , Withanolides/pharmacology , Animals , Caenorhabditis elegans/physiology , Fluoxetine/pharmacology , Gene Knockout Techniques , Molecular Docking Simulation , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Receptors, Serotonin/metabolism , Withania/chemistry
13.
Phytomedicine ; 85: 153476, 2021 May.
Article in English | MEDLINE | ID: covidwho-1051911

ABSTRACT

We present here a new selection criterion for prioritizing research on efficacious drugs for the fight against COVID-19: the relative toxicity versus safety of herbal medications, which were effective against SARS in the 2002/2003 epidemic. We rank these medicines according to their toxicity versus safety as basis for preferential rapid research on their potential in the treatment of COVID-19. The data demonstrate that from toxicological information nothing speaks against immediate investigation on, followed by rapid implementation of Lonicera japonica, Morus alba, Forsythia suspensa, and Codonopsis spec. for treatment of COVID-19 patients. Glycyrrhiza spec. and Panax ginseng are ranked in second priority and ephedrine-free Herba Ephedrae extract in third priority (followed by several drugs in lower preferences). Rapid research on their efficacy in the therapy - as well as safety under the specific circumstances of COVID-19 - followed by equally rapid implementation will provide substantial advantages to Public Health including immediate availability, enlargement of medicinal possibilities, in cases where other means are not successful (non-responders), not tolerated (sensitive individuals) or just not available (as is presently the case) and thus minimize sufferings and save lives. Moreover, their moderate costs and convenient oral application are especially advantageous for underprivileged populations in developing countries.


Subject(s)
Drugs, Chinese Herbal/pharmacology , SARS-CoV-2/drug effects , Animals , COVID-19 , Drugs, Chinese Herbal/toxicity , Humans , Plants, Medicinal/toxicity
14.
Int J Environ Res Public Health ; 18(1)2021 01 05.
Article in English | MEDLINE | ID: covidwho-1021961

ABSTRACT

Opioid abuse and misuse have led to an epidemic which is currently spreading worldwide. Since the number of opioid overdoses is still increasing, it is becoming obvious that current rather unsystematic approaches to tackle this health problem are not effective. This review suggests that fighting the opioid epidemic requires a structured public health approach. Therefore, it is important to consider not only scientific and biomedical perspectives, but societal implications and the lived experience of groups at risk as well. Hence, this review evaluates the risk factors associated with opioid overdoses and investigates the rates of chronic opioid misuse, particularly in the context of chronic pain as well as post-surgery treatments, as the entrance of opioids in people's lives. Linking pharmaceutical biology to narrative analysis is essential to understand the modulations of the usual themes of addiction and abuse present in the opioid crisis. This paper shows that patient narratives can be an important resource in understanding the complexity of opioid abuse and addiction. In particular, the relationship between chronic pain and social inequality must be considered. The main goal of this review is to demonstrate how a deeper transdisciplinary-enriched understanding can lead to more precise strategies of prevention or treatment of opioid abuse.


Subject(s)
Behavior, Addictive , Chronic Pain , Opioid-Related Disorders , Analgesics, Opioid/therapeutic use , Chronic Pain/drug therapy , Chronic Pain/epidemiology , Humans , Opioid Epidemic , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Socioeconomic Factors
15.
Comput Biol Med ; 126: 104046, 2020 11.
Article in English | MEDLINE | ID: covidwho-837907

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is an infectious illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), originally identified in Wuhan, China (December 2019) and has since expanded into a pandemic. Here, we investigate metabolites present in several common spices as possible inhibitors of COVID-19. Specifically, 32 compounds isolated from 14 cooking seasonings were examined as inhibitors for SARS-CoV-2 main protease (Mpro), which is required for viral multiplication. Using a drug discovery approach to identify possible antiviral leads, in silico molecular docking studies were performed. Docking calculations revealed a high potency of salvianolic acid A and curcumin as Mpro inhibitors with binding energies of -9.7 and -9.2 kcal/mol, respectively. Binding mode analysis demonstrated the ability of salvianolic acid A and curcumin to form nine and six hydrogen bonds, respectively with amino acids proximal to Mpro's active site. Stabilities and binding affinities of the two identified natural spices were calculated over 40 ns molecular dynamics simulations and compared to an antiviral protease inhibitor (lopinavir). Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of -44.8, -34.2 and -34.8 kcal/mol, respectively. Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF. This study establishes salvianolic acid A as an in silico natural product inhibitor against the SARS-CoV-2 main protease and provides a promising inhibitor lead for in vitro enzyme testing.


Subject(s)
Betacoronavirus/enzymology , Caffeic Acids/chemistry , Coronavirus Infections/drug therapy , Curcumin/chemistry , Cysteine Endopeptidases , Drug Discovery , Lactates/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , Pneumonia, Viral/drug therapy , Protease Inhibitors/chemistry , Viral Nonstructural Proteins , COVID-19 , Caffeic Acids/therapeutic use , Coronavirus 3C Proteases , Coronavirus Infections/enzymology , Curcumin/therapeutic use , Cysteine Endopeptidases/chemistry , Humans , Lactates/therapeutic use , Pandemics , Pneumonia, Viral/enzymology , Protease Inhibitors/therapeutic use , SARS-CoV-2 , Thermodynamics , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/chemistry
16.
Phytomedicine ; 80: 153337, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-799482

ABSTRACT

BACKGROUND: Throughout the 5000-year history of China, more than 300 epidemics were recorded. Traditional Chinese herbal medicine (TCM) has been used effectively to combat each of these epidemics' infections, and saved many lives. To date, there are hundreds of herbal TCM formulae developed for the purpose of prevention and treatment during epidemic infections. When COVID-19 ravaged the Wuhan district in China in early January 2020, without a deep understanding about the nature of COVID-19, patients admitted to the TCM Hospital in Wuhan were immediately treated with TCM and reported later with >90% efficacy. APPROACH: We conducted conduct a systematic survey of various TCM herbal preparations used in Wuhan and to review their efficacy, according to the published clinical data; and, secondly, to find the most popular herbs used in these preparations and look into the opportunity of future research in the isolation and identification of bioactive natural products for fighting COVID-19. RESULTS: Although bioactive natural products in these herbal preparations may have direct antiviral activities, TCM employed for fighting epidemic infections was primarily based on the TCM theory of restoring the balance of the human immune system, thereby defeating the viral infection indirectly. In addition, certain TCM teachings relevant to the meridian system deserve better attention. For instance, many TCM herbal preparations target the lung meridian, which connects the lung and large intestine. This interconnection between the lung, including the upper respiratory system, and the intestine, may explain why certain TCM formulae showed excellent relief of lung congestion and diarrhea, two characteristics of COVID-19 infection. CONCLUSION: There is good reason for us to learn from ancient wisdom and accumulated clinical experience, in combination with cutting edge science and technologies, to fight with the devastating COVID-19 pandemic now and emerging new coronaviruses in the future.


Subject(s)
Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Plants, Medicinal/chemistry , Antiviral Agents/chemistry , COVID-19/immunology , China , Clinical Trials as Topic , Drugs, Chinese Herbal/chemistry , Humans , Medicine, Chinese Traditional , SARS-CoV-2
17.
Phytomedicine ; 85: 153311, 2021 May.
Article in English | MEDLINE | ID: covidwho-733664

ABSTRACT

BACKGROUND: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge. METHODS: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar). RESULTS: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Hér.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARS-CoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4`-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab. CONCLUSION: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , SARS-CoV-2/drug effects , COVID-19 Vaccines , Clinical Trials as Topic , Drug Evaluation, Preclinical , Humans , Molecular Structure , Pandemics , Plant Preparations/pharmacology
18.
Int J Environ Res Public Health ; 17(16)2020 08 11.
Article in English | MEDLINE | ID: covidwho-705801

ABSTRACT

Lately, myriad of novel viruses have emerged causing epidemics such as SARS, MERS, and SARS-CoV-2, leading to high mortality rates worldwide. Thus, these viruses represented a challenging threat to mankind, especially considering the miniscule data available at our disposal regarding these novel viruses. The entire world established coordinative relations in research projects regarding drug and vaccine development on the external range, whereas on the internal range, all countries declared it an emergency case through imposing different restrictions related to their border control, large gatherings, school attendance, and most social activities. Pandemic combating plans prioritized all sectors including normal people, medical staff politicians, and scientists collectively shouldered the burden. Through planning and learning the previous lessons from SARS and MERS, healthcare systems could succeed in combating the viral spread and implications of these new pandemics. Different management strategies including social distance, social awareness and isolation represented successful ways to slow down the spread of the pandemic. Furthermore, pre-preparedness of some countries for emergencies is crucial to minimize the consequences of the crisis.


Subject(s)
Communicable Disease Control/organization & administration , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Betacoronavirus , COVID-19 , Disaster Planning/organization & administration , Global Health , Humans , SARS-CoV-2
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