Competence of Biopesticide and Neem in Agriculture

Neem plant is considered as the most useful traditional plant in India. The various properties of different parts of neem tree are used as insecticide, antifeedant, hormonal, antifungal, antiallergic, antidermatic, anti-inflammatory, antiscabic larvicidal and spermaticidal activity etc. In recent era the major challenge is to increase the food production without harming the environment and can control the pest. Since, last decades pesticides have become an integral component in sustainable agriculture and the modern day cultivation practices uses of chemical pesticides and fertilizers are in eliminable. Enormous use of different chemical pesticides in agricultural fields is resistant to most of the pests. So that the natural pesticides from A. indica are considered to be less harmful, biodegradability, least persistence, lest toxic to non-target organism, economic and used to combat insects, pests are not ruled out. Neem derived products play an essential role in the pest management, in agricultural fields such as crop and stored grains. Fruitful results of application of formulated neem based products in agriculture field will provide a cost effective technology to the farmers

Molecular modeling and simulations of some antiviral drugs, benzylisoquinoline alkaloid, and coumarin molecules to investigate the effects on Mpro main viral protease inhibition

Background: SARS-CoV-2 is a deadly viral disease and uncounted deaths occurs since its first appearance in the year 2019. The antiviral drugs, benzylisoquinoline alkaloids, and coumarin molecules were searched using different online engines for drug repurposing with SARS-CoV-2 and to investigate the effects on main viral protease (Mpro) upon their bindings. Methods: A database composed of antiviral drugs, benzylisoquinoline alkaloids, and Coumarin molecules was screened through a molecular docking strategy to uncover the interactions of collected molecules with SARS-CoV-2 Mpro. Further, molecular dynamics simulations (MDS) were implemented for 100 ns to calculate the stability of the best complexed molecular scaffold with Mpro. The conformations of the simulated complexes were investigated by using principal component analysis (PCA) and Gibbs energy landscape (FEL) and DSSP together. Next, free binding energy (ΔGbind) was calculated using the mmpbsa method. Results: Molecular docking simulations demonstrate 17 molecules exhibited better binding affinity out of 99 molecules present in the database with the viral protease Mpro, followed ADMET properties and were documented. The Coumarin-EM04 molecular scaffold exhibited interactions with catalytical dyad HIS41, CYS145, and neighboring amino acids SER165 and GLN189 in the catalytical site. The crucial factor RMSD was calculated to determine the orientations of Coumarin-EM04. The Coumarin-EM04 complexed with Mpro was found stable in the binding site during MDS. Furthermore, the free energy binding ΔGbind of Coumarin-EM04 was found to be −187.471 ± 2.230 kJ/mol, and for Remdesivir ΔGbind was −171.926 ± 2.237 kJ/mol with SARS-CoV-2 Mpro. Conclusion: In this study, we identify potent molecules that exhibit interactions with catalytical dyad HIS41 and CYS145 amino acids and unravel Coumarin-EM04 exhibited ΔGbind higher than Remdesivir against Mpro and thus may serve better antiviral agent against SARS-CoV-2

Identification of anti-cyanobacterial leads targeting carbonic anhydrase from phytochemical database using <i>in silico</i> approach

In cyanobacteria, carbonic anhydrase (zinc metalloenzyme) is a major enzyme that converts CO2 to HCO3 maintaining the carbon concentration around the vicinity of RuBisCo, leading to cyanobacterial biomass generation. Anthropogenic activities, disposal of leached micro nutrients effluents from industries into the aquatic environment results in cyanobacterial blooms. The harmful cyanobacteria release cyanotoxins in open-water system which on ingression through oral route causes major health issues like hepatotoxicity and immunotoxicity. A database was prepared consisting of approximately 3k phytochemicals curated from previous literatures, earlier identified by GC-MS analysis. The phytochemicals were subjected to online servers to identify the novel lead molecules which followed ADMET and drug-like candidates. The identified leads were optimized by density functional theory method using B3YLP/G* level of theory. Carbonic anhydrase chosen as target to observe the binding interaction through molecular docking simulations. From the molecules included in the database the highest binding energy exhibited by alpha-tocopherol succinate and mycophenolic acid were found to be -9.23 kcal/mol and -14.41 kcal/mol and displayed interactions with GLY A102, GLN B30, ASP A41, LYS A105 including Zn2+ and their adjacent amino acids CYS 101, HIS 98, CYS 39 in both chain A and chain A-B of carbonic anhydrase. The identified molecular orbitals decipher computed global electrophilicity values (Energy gap, electrophilicity and Softness) of alpha tocopherol succinate and mycophenolic acid were found to be (5.262, 1.948, 0.380) eV and (4.710, 2.805, 0.424) eV demonstrates both molecules are effective and stable. The identified leads may serve as a better anti-carbonic anhydrase agent because they accommodate in the binding site and hampers the catalytic activity of Carbonic anhydrase thus inhibiting the generation of cyanobacterial biomass. This identified lead molecules may serve as a substructure to design novel phytochemicals against carbonic anhydrase present in cyanobacteria. Further in vitro study is necessary to evaluate the efficacy of these molecules

Identification of anti-cyanobacterial leads targeting carbonic anhydrase from phytochemical database using in silico approach

In cyanobacteria, carbonic anhydrase (zinc metalloenzyme) is a major enzyme that converts CO 2 to HCO 3- main¬taining the carbon concentration around the vicinity of RuBisCo, leading to cyanobacterial biomass generation. Anthropogenic activities, disposal of leached micro nutrients effluents from industries into the aquatic en¬viron¬ment results in cyanobacterial blooms. The harmful cyanobacteria release cyanotoxins in open-water system which on ingression through oral route causes major health issues like hepatotoxicity and immunotoxicity. A database was prepared consisting of approximately 3k phytochemicals curated from previous literatures, earlier identified by GC-MS analysis. The phytochemicals were subjected to online servers to identify the novel lead molecules which followed ADMET and drug-like candidates. The identified leads were optimized by density functional theory method using B3YLP/G* level of theory. Carbonic anhydrase chosen as target to observe the binding interaction through molecular docking simulations. From the molecules included in the database the highest binding energy ex¬hibited by alpha-tocopherol succinate and mycophenolic acid were found to be −9.23 kcal/mol and −14.41 kcal/mol and displayed interactions with GLY A102, GLN B30, ASP A41, LYS A105 including Zn 2+ and their adjacent amino acids CYS 101, HIS 98, CYS 39 in both chain A and chain A-B of carbonic anhydrase. The Identified molecular orbitals decipher computed global electrophilicity values (Energy gap, electrophilicity and Softness) of alpha-tocopherol succinate and mycophenolic acid were found to be (5.262, 1.948, 0.380) eV and (4.710, 2.805, 0.424) eV demonstrates both molecules are effective and stable. The identified leads may serve as a better anti-carbonic anhydrase agent because they accommodate in the binding site and hampers the catalytic activity of Carbonic anhydrase thus inhibiting the generation of cyanobacterial biomass. This identified lead mole¬cules may serve as a substructure to design novel phytochemicals against carbonic anhydrase present in cyano¬bacteria. Further in vitro study is necessary to evaluate the efficacy of these molecules

Monte-Carlo Method Based QSAR Model to Discover Phytochemical Urease Inhibitors Using SMILES and GRAPH Descriptors

We developed a Monte-Carlo method basedQSAR model to predict urease inhibiting potency of molecules using SMILES and GRAPHdescriptors on an existing diverse database of urease inhibitors. The QSAR model satisfies allthe statistical parameters required for acceptance as a good model. The model is applied toidentify urease inhibitors among the wide range of compounds in the phytochemical database,NPACT, as a test case. We combine the ligand-based and structure-based drug discoverymethods to improve the accuracy of the prediction. The method predicts pIC50 and estimatesdocking score of compounds in the database. The method may be applied to any other databaseor compounds designed in silico to discover novel drugs targeting urease

Ecological and human health risk associated with heavy metals in sediments and bioaccumulation in some commercially important fishes in Mahanadi River, Odisha, India

Disposal of untreated municipality sewage, industrial wastes and agricultural runoff into the Mahanadi river causes increased heavy metals load in the river basin. The present study assesses the concentrations of heavy metals (Cr, Cd, Hg, Cu, Zn, Pb and As) in sediments and their bioaccumulation in some commercially important fishes. The potential ecological risk of heavy metals in sediments and human health risk associated with the consumption of fish accumulating heavy metals are also evaluated. The concentration of heavy metals measured followed the hierarchy as follows: Mn > Cr > Zn > Cu > Pb > As > Cd > Hg. Potential ecological risk analysis of sediment heavy metal concentrations indicated that four sites in the middle stretch poses moderate ecological risk whereas three sites in the lower stretch posed low ecological risk. Zn showed hyperaccumulation in five different fish species while Cd was observed to be the least bioaccumulative with a hierarchy of Zn > Cu > Pb > Cr > As > Cd. The demersal fish Notepterus notepterus and Clarias batrachus was observed to be the most bio-accumulative to heavy metals. Though potential human health risk assessed using Target Hazard Quotient, Hazard Index and Carcinogenic Risk was found to be within the acceptable threshold, continued disposal of heavy metals could pose a greater carcinogenic as well as non-carcinogenic risk in this region

Molecular Modeling of Novel Fluorophoric Thiazolo- [2, 3-B] Quinazolinones to Study Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition Potency

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) is one of the key regulators that exhibit pivotal role in proliferation of cancer cell. Quinazolinones are studiedly widely as effective EGFR-TK inhibitor because of their higher affinity to bind with adenosine triphosphate (ATP) binding site of receptor tyrosine kinases. However, their toxicity due to non-specific binding to tyrosine kinase in non-cancerous normally dividing cells of the body limits its applicability as a cancer therapeutics. In the present investigation a series of thirty-four novel synthesized thiazolo- [2, 3-b] quinazolinones were studied in silico as EGFR-TK inhibitors. All the thirty-four compounds were screened against EGFR-TK domain using multiple software’s (AutoDock Vina, Argus Lab, YASARA, and MOE). The interactions of the ligands with amino acid residues, namely, Lys721, Met769 and Asp831 of the active site were through the functional groups on aryl substituents at position 3 and 5 of the thiazolo- [2, 3-b] quinazolinone scaffold. The methyl substituents at position 8 of the ligands had prominent hydrophobic interactions in the active site cavity of EGFR-TK domain. The compounds 5ab, 5aq, and 5bq were predicted to be non-toxic and drug-like by in silico ADMET investigations. These compounds were considered for further investigation due to their non-toxicity and higher docking score ranking in different docking methods. The molecular dynamics (MD) simulation for 100 ns of docked complexes revealed the stability of these compounds. The binding free energy determined using Molecular Mechanics Generalized Born Model and Solvent Accessibility (MM-GBSA) method indicate that thiazolo- [2, 3-b] quinazolinone has high inhibitory efficacy similar to the standard drug, erlotinib (5ab - 22.45, 5aq -22.23, 5bq -20.76, and erlotinib -24.11 kcal/mol). In silico studies and MD simulations indicated that compounds (5ab, 5aq and 5bq) could be potential EGFR-TK inhibitors and require further validation as cancer therapeutics using carcinoma cell lines.</p

Table_2_Novel computational and drug design strategies for inhibition of monkeypox virus and Babesia microti: molecular docking, molecular dynamic simulation and drug design approach by natural compounds.DOCX

BackgroundThe alarming increase in tick-borne pathogens such as human Babesia microti is an existential threat to global public health. It is a protozoan parasitic infection transmitted by numerous species of the genus Babesia. Second, monkeypox has recently emerged as a public health crisis, and the virus has spread around the world in the post-COVID-19 period with a very rapid transmission rate. These two novel pathogens are a new concern for human health globally and have become a significant obstacle to the development of modern medicine and the economy of the whole world. Currently, there are no approved drugs for the treatment of this disease. So, this research gap encourages us to find a potential inhibitor from a natural source.Methods and materialsIn this study, a series of natural plant-based biomolecules were subjected to in-depth computational investigation to find the most potent inhibitors targeting major pathogenic proteins responsible for the diseases caused by these two pathogens.ResultsAmong them, most of the selected natural compounds are predicted to bind tightly to the targeted proteins that are crucial for the replication of these novel pathogens. Moreover, all the molecules have outstanding ADMET properties such as high aqueous solubility, a higher human gastrointestinal absorption rate, and a lack of any carcinogenic or hepatotoxic effects; most of them followed Lipinski’s rule. Finally, the stability of the compounds was determined by molecular dynamics simulations (MDs) for 100 ns. During MDs, we observed that the mentioned compounds have exceptional stability against selected pathogens.ConclusionThese advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo studies are necessary to validate their efficacy. Our research highlights the role of Dieckol and Amentoflavone as promising candidates for inhibiting both monkeypox and Babesia microti, demonstrating their multifaceted roles in the control of these pathogens.</p

Table_1_Novel computational and drug design strategies for inhibition of monkeypox virus and Babesia microti: molecular docking, molecular dynamic simulation and drug design approach by natural compounds.DOCX

BackgroundThe alarming increase in tick-borne pathogens such as human Babesia microti is an existential threat to global public health. It is a protozoan parasitic infection transmitted by numerous species of the genus Babesia. Second, monkeypox has recently emerged as a public health crisis, and the virus has spread around the world in the post-COVID-19 period with a very rapid transmission rate. These two novel pathogens are a new concern for human health globally and have become a significant obstacle to the development of modern medicine and the economy of the whole world. Currently, there are no approved drugs for the treatment of this disease. So, this research gap encourages us to find a potential inhibitor from a natural source.Methods and materialsIn this study, a series of natural plant-based biomolecules were subjected to in-depth computational investigation to find the most potent inhibitors targeting major pathogenic proteins responsible for the diseases caused by these two pathogens.ResultsAmong them, most of the selected natural compounds are predicted to bind tightly to the targeted proteins that are crucial for the replication of these novel pathogens. Moreover, all the molecules have outstanding ADMET properties such as high aqueous solubility, a higher human gastrointestinal absorption rate, and a lack of any carcinogenic or hepatotoxic effects; most of them followed Lipinski’s rule. Finally, the stability of the compounds was determined by molecular dynamics simulations (MDs) for 100 ns. During MDs, we observed that the mentioned compounds have exceptional stability against selected pathogens.ConclusionThese advanced computational strategies reported that 11 lead compounds, including dieckol and amentoflavone, exhibited high potency, excellent drug-like properties, and no toxicity. These compounds demonstrated strong binding affinities to the target enzymes, especially dieckol, which displayed superior stability during molecular dynamics simulations. The MM/PBSA method confirmed the favorable binding energies of amentoflavone and dieckol. However, further in vitro and in vivo studies are necessary to validate their efficacy. Our research highlights the role of Dieckol and Amentoflavone as promising candidates for inhibiting both monkeypox and Babesia microti, demonstrating their multifaceted roles in the control of these pathogens.</p