Screening of potential drug from Azadirachta Indica (Neem) extracts for SARS-CoV-2: An insight from molecular docking and MD-simulation studies.
Ontology highlight
ABSTRACT:
SUBMITTER: Baildya N
PROVIDER: S-EPMC7532348 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:This data article provides gene expression profiles, determined by using real-time PCR, of fibroblasts and keratinocytes treated with 0.01% and 0.001% extracts of neem plant (Azadirachta indica), local name "Kohomba" in Sri Lanka, harvested in Sri Lanka. For fibroblasts, the dataset includes expression profiles for genes encoding hyaluronan synthase 1 (HAS1), hyaluronan synthase 2 (HAS2), hyaluronidase-1 (HYAL1), hyaluronidase-2 (HYAL2), versican, aggrecan, CD44, collagen, type I, alpha 1 (COL1A1), collagen, type III, alpha 1 (COL3A1), collagen, type VII, alpha 1 (COL7A1), matrix metalloproteinase 1 (MMP1), acid ceramidase, basic fibroblast growth factor (bFGF), fibroblast growth factor-7 (FGF7), vascular endothelial growth factor (VEGF), interleukin-1 alpha (IL-1α), cyclooxygenase-2 (cox2), transforming growth factor beta (TGF-β), and aquaporin 3 (AQP3). For keratinocytes, the expression profiles are for genes encoding HAS1, HAS2, HYAL1, HYAL2, versican, CD44, IL-1α, cox2, TGF-β, AQP3, Laminin5, collagen, type XVII, alpha 1 (COL17A1), integrin alpha-6 (ITGA6), ceramide synthase 3 (CERS3), elongation of very long chain fatty acids protein 1 (ELOVL1), elongation of very long chain fatty acids protein 4 (ELOVL4), filaggrin (FLG), transglutaminase 1 (TGM1), and keratin 1 (KRT1). The expression profiles are provided as bar graphs.
| S-EPMC5752095 | biostudies-literature
Project description:The rapid global spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has created an unprecedented healthcare crisis. The treatment for the severe respiratory illness caused by this virus is primarily symptomatic at this point, although the usage of a broad antiviral drug Remdesivir has been allowed on emergency basis by the Food and Drug Administration (FDA).The ever-increasing death toll highlights an urgent need for development of specific antivirals. In this work, we have utilized docking and simulation methods to identify small molecule inhibitors of SARS-CoV-2 Membrane (M) and Envelope (E) proteins, which are essential for virus assembly and budding. A total of 70 compounds from an Indian medicinal plant source (Azadirachta indica or Neem) were virtually screened against these two proteins and further analyzed with molecular dynamics simulations, which resulted in the identification of a few common compounds with strong binding to both structural proteins. The compounds bind to biologically critical regions of M and E, indicating their potential to inhibit the functionality of these components. We hope that our computational approach may result in the identification of effective inhibitors of SARS-CoV-2 assembly.
| S-EPMC7311162 | biostudies-literature
Project description:Diabetes Mellitus is affecting people of all age groups worldwide. Many synthetic medicines available for type 2 diabetes mellitus in the market. However, there is a strong requirement for the development of better anti-diabetes compounds sourced especially from natural sources like medicinal plants. The extracts from the leaves of neem (Azadirachta indica) is traditionally known to have anti-diabetes properties. Therefore, there is an increased interest to identify potential compounds identified from neem leaf extracts showing predicted binding property with the known diabetes mellitus type 2 protein enzyme target phosphoenol-pyruvate carboxykinase(PEPCK). The structure data for compounds found in the leaf extract of neem was screened against PEPCK using molecular docking simulation and screening techniques. Results show that the compound 3-Deacetyl-3-cinnamoyl-azadirachtin possesses best binding properties with PEPCK. This observation finds application for further consideration in in vitro and in vivo validation.
| S-EPMC3910360 | biostudies-literature
Project description:Neem (Azadirachta indica A. Juss) oil (NO) was assayed against forty-eight isolates of Escherichia coli by standardised disc diffusion test and microdilution test. By molecular biology characterization, fourteen isolates resulted in diarrheagenic E. coli with sixteen primer pairs that specifically amplify unique sequences of virulence genes and of 16S rRNA. The NO showed biological activity against all isolates. The bacterial growth inhibition zone by disc diffusion method (100?µL NO) ranged between 9.50 ± 0.70 and 30.00 ± 1.00?mm. The antibacterial activity was furthermore determined at lower NO concentrations (1?:?10-1?:?10,000). The percent of growth reduction ranged between 23.71 ± 1.00 and 99.70 ± 1.53. The highest bacterial growth reduction was 1?:?10 NO concentration with 50?µL of bacterial suspension (ca. 1 × 10(6)?CFU/mL). There is significant difference between the antibacterial activities against pathogenic and nonpathogenic E. coli, as well as NO and ciprofloxacin activities. Viable cells after the different NO concentration treatments were checked by molecular biology assay using PMA dye. On the basis of the obtained results, NO counteracts E. coli and also influences the virulence of E. coli viable cells after NO treatment. The NO metabolomic composition was obtained using fingerprint HPTLC.
| S-EPMC4433627 | biostudies-literature
Project description:In this study, we prepared, characterized, and performed toxicity analyses of poly(?-caprolactone) nanocapsules loaded with neem oil. Three formulations were prepared by the emulsion/solvent evaporation method. The nanocapsules showed a mean size distribution around 400?nm, with polydispersity below 0.2 and were stable for 120 days. Cytotoxicity and genotoxicity results showed an increase in toxicity of the oleic acid?+?neem formulations according to the amount of oleic acid used. The minimum inhibitory concentrations demonstrated that all the formulations containing neem oil were active. The nanocapsules containing neem oil did not affect the soil microbiota during 300 days of exposure compared to the control. Phytotoxicity studies indicated that NC_20 (200?mg of neem oil) did not affect the net photosynthesis and stomatal conductance of maize plants, whereas use of NC_10 (100:100 of neem:oleic acid) and NC_15 (150:50 of neem:oleic acid) led to negative effects on these physiological parameters. Hence, the use of oleic acid as a complement in the nanocapsules was not a good strategy, since the nanocapsules that only contained neem oil showed lower toxicity. These results demonstrate that evaluation of the toxicity of nanopesticides is essential for the development of environmentally friendly formulations intended for applications in agriculture.
| S-EPMC5517525 | biostudies-literature
Project description:Objective:To evaluate antibacterial and cytotoxic effect of 2 methanolic extracts of Azadirachta indica and Moringa oleifera against strains of Enterococcus faecalis (ATCC 29212) in vitro. Methods:The methanolic extracts of Azadirachta indica and Moringa oleifera were prepared in vitro. The antibacterial effect of the extracts against Enterococcus faecalis was evaluated using the agar diffusion technique. The minimum inhibitory concentration (MIC) was determined using the microdilution method and the cytotoxicity using the cellular line MDCK. Results:The methanolic extract with the most antibacterial effect during the first 24 and 48 hours against Enterococcus faecalis was Moringa oleifera, evidencing a growth inhibition zone of 35.5?±?1.05 and 44.83?±?0.98, respectively. The MIC for both extracts was 75?µg/ml. The bactericidal effect of the Azadirachta indica extract was found at a concentration of 25?µg/ml and a concentration of 75?µg/ml for Moringa extract. Conclusions:In conclusion, we demonstrated that the methanolic extract of Azadirachta indica and Moringa oleifera both have an antibacterial effect against Enterococcus faecalis strains during the first 24 and 48 hours. None of the extracts exhibited toxicity against the cell lines under low concentrations.
| S-EPMC6176315 | biostudies-literature
Project description:Different strains of influenza virus are affecting a large number of people worldwide. Many synthetic antiviral medicines are available for influenza virus in the market. But still there is a need for the development of universal drugs against these strains of influenza virus.For this purpose conserved residues within the influenza virus nucleoprotein have been retrieved. The drugs, previously known to have antiviral properties, were screened to identify the best candidate universal drug against Influenza virus strains. Compounds from leaf extracts of neem, were also screened to identify the natural drugs without side effects.Molecular docking identified three potential compounds (Nimbaflavone, Rutin, and Hyperoside) having perfect binding with reported conserved residues (ASP302, SER50) of influenza virus nucleoprotein that is involved in the binding of drugs. Further analysis showed Hyperoside as a universal drug against various influenza strains. Some chemical drugs were also evaluated through screening against nucleoprotein. The results showed six drugs (OMS, CBX, LGH, Naproxen, BMS-883559, and BMS-885838) which were interacting with same conserved residues (ASP302, TYR52, SER50, GLY288, SER376, and ARG99) as were found in the case of neem phytochemicals. Hyperoside from neem leaf extract along with drugs LGH, Naproxen, BMS-885838, and BMS-883559 showed best interactions with conserved residues of nucleoprotein.The compound Hyperoside from neem leaf extract along with drugs LGH, Naproxen, BMS-885838, and BMS-883559 showed best interactions with conserved residues of nucleoprotein. So these compounds have been identified for their potential against influenza strains to be utilized as a universal drug.
| S-EPMC5162082 | biostudies-literature
Project description:Porcine reproductive and respiratory syndrome virus (PRRSV) is a global health problem for pigs. PRRSV is highly destructive and responsible for significant losses to the swine industry. Vaccines are available but incapable of providing adequate and long-term protection. As a result, effective and safe strategies are urgently needed to combat the virus. The scavenger receptor cysteine-rich domain 5 (SRCR5) in porcine CD163, non-structural protein 4 (Nsp4), and Nsp10 are known to play significant roles in PRRSV infection and disease development. Therefore, we targeted these proteins to identify multi-target antiviral compounds. To identify potent inhibitors, molecular docking of neem phytochemicals was conducted; three compounds [7-deacetyl-7-oxogedunin (CID:1886), Kulactone (CID:15560423), and Nimocin (CASID:104522-76-1)] were selected based on the lowest binding energy and multi-target inhibitory nature. The efficacy and safety of the selected compounds were revealed through the pharmacokinetics analysis and toxicity assessment. Moreover, 100 ns molecular dynamics (MD) simulation was performed to evaluate the stability and dynamic behavior of target proteins and their docked complexes with selected compounds. Besides, molecular mechanics Poisson-Boltzmann surface area method was used to estimate the binding free energy of each protein-ligand complex obtained from the MD simulations and validate the affinities of selected compounds to target proteins. Based on our analysis, we concluded that the identified multi-target compounds can be utilized as lead compounds for the development of natural drugs against PRRSV. If further validated in clinical studies, these compounds can be used individually or in combination against the virus.
| S-EPMC9244183 | biostudies-literature
Project description:Human pancreatic ?-amylase (HPA) inhibitors offer an effective strategy to lower postprandial hyperglycemia via control of starch breakdown. Limonoids from Azadirachta indica known for their therapeutic potential were screened for pancreatic ?-amylase inhibition, a known anti-diabetic target. Studies were carried out to reveal their mode of action so as to justify their hypoglycemic potential. Of the nine limonoids isolated/semi-synthesized from A.indica and screened for ?-amylase inhibition, azadiradione and exhibited potential inhibition with an IC50 value of 74.17 and 68.38 ?M, respectively against HPA under in vitro conditions. Further screening on AR42J ?-amylase secretory cell line for cytotoxicity and bioactivity revealed that azadiradione and gedunin exhibited cytotoxicity with IC50 of 11.1 and 13.4?M. Maximal secreted ?-amylase inhibition of 41.8% and 53.4% was seen at 3.5 and 3.3?M, respectively. Michaelis-Menten kinetics suggested a mixed mode of inhibition with maltopentaose (Ki 42.2, 18.6 ?M) and starch (Ki' 75.8, 37.4 ?M) as substrate with a stiochiometry of 1:1 for both azadiradione and gedunin, respectively. The molecular docking simulation indicated plausible ?-alkyl and alkyl-alkyl interactions between the aromatic amino acids and inhibitors. Fluorescence and CD confirmed the involvement of tryptophan and tyrosine in ligand binding to HPA. Thermodynamic parameters suggested that binding is enthalpically and entropically driven with ?G° of -21.25 kJ mol-1 and -21.16 kJ mol-1 for azadiradione and gedunin, respectively. Thus, the limonoids azadiradione and gedunin could bind and inactivate HPA (anti-diabetic target) and may prove to be lead drug candidates to reduce/control post-prandial hyperglycemia.
| S-EPMC4607367 | biostudies-literature
Project description:BackgroundNeem tree (Azadirachta indica) is one of the richest sources of skeletally diverse triterpenoids and they are well-known for their broad-spectrum pharmacological and insecticidal properties. However, the abundance of Neem triterpenoids varies among the tissues. Here, we delineate quantitative profiling of fifteen major triterpenoids across various tissues including developmental stages of kernel and pericarp, flower, leaf, stem and bark using UPLC-ESI(+)-HRMS based profiling. Transcriptome analysis was used to identify the initial genes involved in isoprenoid biosynthesis. Based on transcriptome analysis, two short-chain prenyltransferases and squalene synthase (AiSQS) were cloned and functionally characterized.ResultsQuantitative profiling revealed differential abundance of both total and individual triterpenoid content across various tissues. RNA from tissues with high triterpenoid content (fruit, flower and leaf) were pooled to generate 79.08 million paired-end reads using Illumina GA ΙΙ platform. 41,140 transcripts were generated by d e novo assembly. Transcriptome annotation led to the identification of the putative genes involved in isoprenoid biosynthesis. Two short-chain prenyltransferases, geranyl diphosphate synthase (AiGDS) and farnesyl diphosphate synthase (AiFDS) and squalene synthase (AiSQS) were cloned and functionally characterized using transcriptome data. RT-PCR studies indicated five-fold and ten-fold higher relative expression level of AiSQS in fruits as compared to leaves and flowers, respectively.ConclusionsTriterpenoid profiling indicated that there is tissue specific variation in their abundance. The mature seed kernel and initial stages of pericarp were found to contain the highest amount of limonoids. Furthermore, a wide diversity of triterpenoids, especially C-seco triterpenoids were observed in kernel as compared to the other tissues. Pericarp, flower and leaf contained mainly ring-intact triterpenoids. The initial genes such as AiGDS, AiFDS and AiSQS involved in the isoprenoids biosynthesis have been functionally characterized. The expression levels of AiFDS and AiSQS were found to be in correlation with the total triterpenoid content in individual tissues.
| S-EPMC4559364 | biostudies-literature