In silico screening of potent bioactive compounds from honeybee products against COVID-19 target enzymes.
Ontology highlight
ABSTRACT:
SUBMITTER: Shaldam MA
PROVIDER: S-EPMC8088405 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Honeybees produce honey, royal jelly, propolis, bee venom, bee pollen, and beeswax, which potentially benefit to humans due to the bioactives in them. Clinical standardization of these products is hindered by chemical variability depending on honeybee and botanical sources, but different molecules have been isolated and pharmacologically characterized. Major honey bioactives include phenolics, methylglyoxal, royal jelly proteins (MRJPs), and oligosaccharides. In royal jelly there are antimicrobial jelleins and royalisin peptides, MRJPs, and hydroxy-decenoic acid derivatives, notably 10-hydroxy-2-decenoic acid (10-HDA), with antimicrobial, anti-inflammatory, immunomodulatory, neuromodulatory, metabolic syndrome preventing, and anti-aging activities. Propolis contains caffeic acid phenethyl ester and artepillin C, specific of Brazilian propolis, with antiviral, immunomodulatory, anti-inflammatory and anticancer effects. Bee venom consists of toxic peptides like pain-inducing melittin, SK channel blocking apamin, and allergenic phospholipase A2. Bee pollen is vitaminic, contains antioxidant and anti-inflammatory plant phenolics, as well as antiatherosclerotic, antidiabetic, and hypoglycemic flavonoids, unsaturated fatty acids, and sterols. Beeswax is widely used in cosmetics and makeup. Given the importance of drug discovery from natural sources, this review is aimed at providing an exhaustive screening of the bioactive compounds detected in honeybee products and of their curative or adverse biological effects.
| S-EPMC5487425 | biostudies-literature
Project description:In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
| S-EPMC7042511 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19), resulting from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can cause severe and fatal pneumonia along with other life-threatening complications. The COVID-19 pandemic has taken a heavy toll on the healthcare system globally and has hit the economy hard in all affected countries. As a result, there is an unmet medical need for both the prevention and treatment of COVID-19 infection. Several herbal remedies have claimed to show promising clinical results, but the mechanisms of action are not clear. We set out to identify the anti-viral natural products of these herbal remedies that presumably inhibit the life cycle of SARS-CoV-2. Particularly we chose four key SARS-CoV-2 viral enzymes as targets: Papain-like protease, Main protease, RNA dependent RNA polymerase, and 2'-O-ribose methyltransferase, which were subjected to an unbiased in silico screening against a small molecule library of 33,765 compounds originating from herbs and medicinal plants. The small molecules were then ranked based on their free energy of fitting into the "druggable" pockets on the surface of each target protein. We have analyzed the best "fit" molecules and annotated them according to their plant sources and pharmacokinetic properties. Here we present a list of potential anti-viral ingredients of herbal remedies targeting SARS-CoV-2 and explore the potential mechanisms of action of these compounds as a framework for further development of chemoprophylaxis agents against COVID-19.
| S-EPMC8310681 | biostudies-literature
Project description:BACKGROUND:The prolonged use of antibiotic viz., tetracycline, quinolones, ampicillin, etc., to reduce the infection of cholera, may failed due to the emergence of new Vibrio cholerae antibiotics resistant strains. Moreover, these antibiotics even restricted for patient suffering from severe dehydration. Hence, there is a call to find an alternative therapeutics against V. cholerae. The natures serve different herbs in its lap which might contain several natural therapeutic compounds almost all diseases. Computer-aided designing is the initial steps for screening the novel inhibitors. OBJECTIVE:To identify and evaluate natural compounds with low side effects with high efficacy against V. cholerae has been done. MATERIALS AND METHODS:In silico screening, absorption, digestion, metabolism, and excretion (ADME), and docking of herbal compounds have been performed on to the target ToxT (transcriptional activator of V. cholerae). The compound with good ADME properties and drug-likeness property were subjected to docking. RESULTS:From 70 herbal compounds, some compounds such as aloin, campesterol, lupeol, and ursolic acid showed a violation of the rule of five and compounds such as lupeol and beta carotene showed negative binding energy. Luteolin, catechin, brevifolin, etc., compounds were selected based on ADME, drug-likeness property, and docking studies. CONCLUSION:Two compounds named catechin and luteolin showed better inhibition properties against ToxT and good ADME and drug-likeness property were selected as a better lead molecule for drug development in future. The Genetic Optimization for Ligand Docking fitness score for catechin is 48.74 kcal/mol and luteolin 38.12 kcal/mol. SUMMARY:Vibrio cholerae became antibiotic resistance and associated with several cholera epidemic and pandemic. Hence, there is a need to find an alternative therapeutics against V. cholerae. Many herbal compounds present in nature having high medicinal value. From in-silico study, found two compound Luteolin from Tulsi and Catechin from Green Tea which showed good binding energy and druggish property. Abbreviations used: V. cholerae: Vibrio cholera, ADME: Absorption, digestion, metabolism and excretion, CT: Cholera toxin, TCP: Toxin co-regulated Pilus, GOLD: Genetic Optimization for Ligand Docking, Asp: Aspartic acid, Arg: Arginine, Lys: Lysine, Thr: Threonine, Tyr: Tyrosine, KEGG: Kyoto encyclopedia of Genes and Genomes.
| S-EPMC4787087 | biostudies-literature
Project description:Cancer is a devastating disease that has claimed many lives. Natural bioactive agents from plants are gaining wide attention for their anticancer activities. Several studies have found that natural plant-based bioactive compounds can enhance the efficacy of chemotherapy, and in some cases ameliorate some of the side-effects of drugs used as chemotherapeutic agents. In this paper, we have reviewed the literature on the anticancer effects of four plant-based bioactive compounds namely, curcumin, myricetin, geraniin and tocotrienols (T3) to provide an overview on some of the key findings that are related to this effect. The molecular mechanisms through which the active compounds may exert their anticancer properties in cell and animal-based studies also discussed.
| S-EPMC6995630 | biostudies-literature
Project description:AbstractBreast cancer is one of the leading causes of death among women. We employed in silico model to predict the mechanism of actions of selected novel compounds reported against breast cancer using ADMET profiling, drug likeness and molecular docking analyses. The selected compounds were andrographolide (AGP), dipalmitoylphosphatidic acid (DPA), 3-(4-Bromo phenylazo)-2,4-pentanedione (BPP), atorvastatin (ATS), benzylserine (BZS) and 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD). These compounds largely conform to ADMETlab and Lipinki's rule of drug likeness criteria in addition to their lesser hepatotoxic and mutagenic effects. Docking studies revealed a strong affinity of AGP versus NF-kB (- 6.8 kcal/mol), DPA versus Cutlike-homeobox (- 5.1 kcal/mol), BPP versus Hypoxia inducing factor 1 (- 7.7 kcal/mol), ATS versus Sterol Regulatory Element Binding Protein 2 (- 7.2 kcal/mol), BZS versus Ephrin type-A receptor 2 (- 4.4 kcal/mol) and TCD versus Ying Yang 1 (- 9.4 kcal/mol). Likewise, interaction between the said compounds and respective gene products were evidently observed with strong affinities; AGP versus COX-2 (- 9.6 kcal/mol), DPA versus Fibroblast growth factor receptor (- 5.9 kcal/mol), BPP versus Vascular endothelial growth factor (- 5.8 kcal/mol), ATS versus HMG-COA reductase (- 9.1 kcal/mol), BZS versus L-type amino acid transporter 1 (- 5.3 kcal/mol) and TCD versus Histone deacytylase (- 7.7 kcal/mol), respectively. The compounds might potentially target transcription through inhibition of promoter-transcription factor binding and/or inactivation of final gene product. Thus, findings from this study provide a possible mechanism of action of these xenobiotics to guide in vitro and in vivo studies in breast cancer.Graphic abstract
| S-EPMC7652978 | biostudies-literature
Project description:Background During the second wave of the COVID-19 pandemic, an unusual increase in cases of mucormycosis was observed in India, owing to immunological dysregulation caused by the SARS-CoV-2 and the use of broad-spectrum antibiotics, particularly in patients with poorly controlled diabetes with ketoacidosis to have contributed to the rise, and it has been declared an epidemic in several states of India. Because of the black colouring of dead and dying tissue caused by the fungus, it was dubbed "black fungus" by several Indian media outlets. In this study, attempts were taken to unmask novel therapeutic options to treat mucormycosis disease. Rhizopus species is the primary fungi responsible for 70% of mucormycosis cases. Results We chose three important proteins from the Rhizopus delemar such as CotH3, Lanosterol 14 alpha-demethylase and Mucoricin which plays a crucial role in the virulence of Mucorales. Initially, we explored the physiochemical, structural and functional insights of proteins and later using AutoDock Vina, we applied computational protein–ligand binding modelling to perform a virtual screening around 300 selected compounds against these three proteins, including FDA-approved drugs, FDA-unapproved drugs, investigational-only drugs and natural bioactive compounds. ADME parameters, toxicity risk and biological activity of those compounds were approximated via in silico methods. Our computational studies identified six ligands as potential inhibitors against Rhizopus delemar, including 12,28-Oxamanzamine A, vialinin B and deoxytopsentin for CotH3; pramiconazole and saperconazole for Lanosterol 14 alpha-demethylase; and Hesperidin for Mucoricin. Interestingly, 12,28-Oxamanzamine A showed a maximum binding affinity with all three proteins (CotH3: − 10.2 kcal/mol Lanosterol 14 alpha-demethylase: − 10.9 kcal/mol Mucoricin: − 8.6 kcal/mol). Conclusions In summary, our investigation identified 12,28-Oxamanzamine A, vialinin B, deoxytopsentin, pramiconazole, saperconazole and hesperidin as potent bioactive compounds for treating mucormycosis that may be considered for further optimisation techniques and in vitro and in vivo studies. Supplementary Information The online version contains supplementary material available at 10.1186/s42269-022-00704-4.
| S-EPMC8802264 | biostudies-literature
Project description:The discovery of novel synthetic compounds with drug-like properties is an ongoing challenge in medicinal chemistry. Natural products have inspired the synthesis of compounds for pharmaceutical application, most of which are based on N-heterocyclic motifs. Among these, the pyrrole ring is one of the most explored heterocycles in drug discovery programs for several therapeutic areas, confirmed by the high number of pyrrole-based drugs reaching the market. In the present review, we focused on pyrrole and its hetero-fused derivatives with anticancer, antimicrobial, and antiviral activities, reported in the literature between 2015 and 2019, for which a specific target was identified, being responsible for their biological activity. It emerges that the powerful pharmaceutical and pharmacological features provided by the pyrrole nucleus as pharmacophore unit of many drugs are still recognized by medicinal chemists.
| S-EPMC7455853 | biostudies-literature
Project description:Benzalacetophenones, precursors of flavonoids are aromatic ketones and enones and possess the immunostimulant as well as antiviral activities. Thus, benzalacetophenones were screened against the COVID-19 that could be lethal in patients with compromised immunity. We considered ChEBI recorded benzalacetophenone derivative(s) and evaluated their activity against 3C-like protease (3CLpro), papain-like protease (PLpro), and spike protein of SARS-Cov-2 to elucidate their possible role as antiviral agents. The probable targets for each compound were retrieved from DIGEP-Pred at 0.5 pharmacological activity and all the modulated proteins were enriched to identify the probably regulated pathways, biological processes, cellular components, and molecular functions. In addition, molecular docking was performed using AutoDock 4 and the best-identified hits were subjected to all-atom molecular dynamics simulation and binding energy calculations using molecular mechanics Poisson-Boltzmann surface area (MMPBSA). The compound 4-hydroxycordoin showed the highest druglikeness score and regulated nine proteins of which five were down-regulated and four were upregulated. Similarly, enrichment analysis identified the modulation of multiple pathways concerned with the immune system as well as pathways related to infectious and non-infectious diseases. Likewise, 3'-(3-methyl-2-butenyl)-4'-O-β-d-glucopyranosyl-4,2'-dihydroxychalcone with 3CLpro, 4-hydroxycordoin with PLpro and mallotophilippen D with spike protein receptor-binding domain showed highest binding affinity, revealed stable interactions during the simulation, and scored binding free energy of -26.09 kcal/mol, -16.28 kcal/mol, and -39.2 kcal/mol, respectively. Predicted anti-SARS-CoV-2 activities of the benzalacetophenones reflected the requirement of wet lab studies to develop novel antiviral candidates.
| S-EPMC9135652 | biostudies-literature
Project description:Sirtuin type 1 (SIRT1) belongs to the family of NAD(+) dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs), as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP). The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1.
| S-EPMC4766345 | biostudies-literature