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•A novel green synthesis method is employed for the synthesis of copper nanoparticles.•The average size of the synthesized Cu nanoparticles is in the range of 5–25 nm.•The obtained ...nanoparticles have shown good antibacterial activity against gram-positive and gram-negative bacteria.
In the present report, for the first time aqueous extract of Curcuma longa powder is used for the synthesis of Copper nanoparticles (Cu NPs) using a simple and cost effective method. Morphology, size, crystallinity, composition and microstructure of the synthesized Cu Nps are studied. Size of the particles are in the range of 5–20 nm. In addition to the above, antibacterial activity of the obtained Cu NPs is tested for both gram-positive and gram-negative microorganisms. Zone of inhibition of Cu NPs for gram positive bacteria is more compared to gram negative bacteria. The current work on green synthesis of metallic nanoparticles can be considered as an alternative method to avoid the usage of hazardous compounds and bitter reaction conditions in the production of metal nanoparticles. The obtained Cu NPs with their distinctive structural properties and effective biological effects can be used in applications viz. antimicrobial, antifungal, anticancer activity.
Deguelin is a major active ingredient and principal component in several plants and it is a potential molecule to target proteins of cancer cell signaling pathway. As a complex natural extract, ...deguelin interacts with various molecular targets to exert its anti-tumor properties at nanomolar level. It induces cell apoptosis by blocking anti-apoptotic pathways, while inhibiting tumor cell multiplication and malignant transformation through p27-cyclin-E-pRb-E2F1- cell cycle control and HIF-1alphaVEGF antiangiogenic pathways. In silico studies of deguelin and its derivatives is performed to explore interactions with Cyclin D1 and Cyclin E to understand the molecular insights of derivatives with the receptors. Deguelin and its derivatives are minimized by Avogadro to achieve stable conformation. All docking simulation are performed with AutoDockVina and virtual screening of docked ligands are carried out based on binding energy and number of hydrogen bonds. Molecular dynamics (MD) and Simulation of Cyclin D1 and Cyclin E1 is performed for 100 ns and stable conformation is obtained at 78 ns and 19 ns respectively. Ligands thus obtained from docking studies may be probable target to inhibit cancer cell signaling pathways.
The outbreak of novel coronavirus (COVID-19), which began from Wuhan City, Hubei, China, and declared as a Public Health Emergency of International Concern by World Health Organization (WHO) on 30
...January 2020. The present study describes how the available drug candidates can be used as a potential SARS-CoV-2 M
inhibitor by molecular docking and molecular dynamic simulation studies. Drug repurposing strategy is applied by using the library of antiviral and FDA approved drugs retrieved from the Selleckchem Inc. (Houston, TX, http://www.selleckchem.com) and DrugBank database respectively. Computational methods like molecular docking and molecular dynamics simulation were used. The molecular docking calculations were performed using LeadIT FlexX software. The molecular dynamics simulations of 100 ns were performed to study conformational stability for all complex systems. Mitoxantrone and Leucovorin from FDA approved drug library and Birinapant and Dynasore from anti-viral drug libraries interact with SARS-CoV-2 M
at higher efficiency as a result of the improved steric and hydrophobic environment in the binding cavity to make stable complex. Also, the molecular dynamics simulations of 100 ns revealed the mean RMSD value of 2.25 Å for all the complex systems. This shows that lead compounds bound tightly within the M
cavity and thus having conformational stability. Glutamic acid (Glu166) of M
is a key residue to hold and form a stable complex of reported lead compounds by forming hydrogen bonds and salt bridge. Our findings suggest that Mitoxantrone, Leucovorin, Birinapant, and Dynasore represents potential inhibitors of SARS-CoV-2 M
.
A recent surge in finding new candidate vaccines and potential antivirals to tackle atypical pneumonia triggered by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) needs new ...and unexplored approaches in solving this global pandemic. The homotrimeric transmembrane spike (S) glycoprotein of coronaviruses which facilitates virus entry into the host cells is covered with N-linked glycans having oligomannose and complex sugars. These glycans provide a unique opportunity for their targeting via carbohydrate-binding agents (CBAs) which have shown their antiviral potential against coronaviruses and enveloped viruses. However, CBA-ligand interaction is not fully explored in developing novel carbohydrate-binding-based antivirals due to associated unfavorable responses with CBAs. CBAs possess unique carbohydrate-binding specificity, therefore, CBAs like mannose-specific plant lectins/lectin-like mimic Pradimicin-A (PRM-A) can be used for targeting N-linked glycans of S glycoproteins. Here, we report studies on the binding and stability of lectins (NPA, UDA, GRFT, CV-N and wild-type and mutant BanLec) and PRM-A with the S glycoprotein glycans via docking and MD simulation. MM/GBSA calculations were also performed for docked complexes. Interestingly, stable BanLec mutant (H84T) also showed similar docking affinity and interactions as compared to wild-type BanLec, thus, confirming that uncoupling the mitogenic activity did not alter the lectin binding activity of BanLec. The stability of the docked complexes, i.e. PRM-A and lectins with SARS-CoV-2 S glycoprotein showed favorable intermolecular hydrogen-bond formation during the 100 ns MD simulation. Taking these together, our predicted in silico results will be helpful in the design and development of novel CBA-based antivirals for the SARS-CoV-2 neutralization.
Communicated by Ramaswamy H. Sarma
The overexpression of cyclin D1 and cyclin E due to their oncogenic potential and amplification has been associated with a higher mortality rate in many cancers. The deguelin is a natural compound, ...has shown promising anti-cancer activity by directly binding cyclin D1 and cyclin E and thus suppressing its function. The C7a atomic position of deguelin structure contains a proton that generates stabilized radical, as a result, decomposed deguelin reduces its structural stability and significantly decreases its biological activity. To design deguelin derivatives with the reduced potential side effect, series of B, C-ring truncated derivatives were investigated as cyclin D1 and cyclin E inhibitors. R-group-based enumeration was implemented in the deguelin scaffold using the R-group enumeration module of Schrödinger. Drug-Like filters like, REOS and PAINs series were applied to the enumerated compound library to remove compounds containing reactive functional groups. Further, screened compounds were docked within the ligand-binding cavity of cyclin D1 and cyclin E crystal structure, using Glide SP and XP protocol to obtain docking poses. Enrichment calculations were done using SchrÖdinger software, with 1000 decoy compounds (from DUD.E database) and 60 compounds (XP best poses) along with deguelin, to validate the docking protocol. The receiver operating characteristic (ROC) curve indicates
R
2
= 0.94 for cyclin D1 and
R
2
= 0.79 for cyclin E, suggesting that the docking protocol is valid. Besides, we explored molecular dynamics simulation to probe the binding stability of deguelin and its derivatives within the binding cavity of cyclin D1 and cyclin E structures which are associated with the cyclin D1 and cyclin E inhibitory mechanism.
Graphic abstract
Flavanone compounds are naturally occurring phytochemicals present in most of citrus fruits reported to be a potential anticancer moiety as it majorly participates in the inhibition of the cell ...cycle, apoptosis, and angiogenesis. Because of poor bioavailability, natural flavanones were not used as therapeutic targets so flavanone congeners were prepared by modifying at B-functional group using compound libraries such as PubChem Database. Cyclin-dependent kinase is primarily activating the cell cycle and potentiating the M phase, in order to control the cell cycle in cancer cyclin-dependent pathway was targeted and potential cyclin D/CDK4 receptor protein was retrieved from Protein Data Bank (PDBID:2W9Z). The binding site was determined using FlexX docking. Flavanone and its congeners were docked against the 2W9Z receptor protein with the docking software FlexX. For validation of docking results, molecular dynamics simulations of the best-fitting molecule were carried out using Desmond Package. Noncovalent interactions like hydrogen bonds, electrostatic interaction, and Van der walls potentials for stable conformations were calculated. Thus, upon docking and molecular dynamics studies, we discovered the potential flavanone derivatives such as Flavanone 20, Flavanone 25, and Flavanone 29, will become a potential drug target in controlling cell cycle arrest and may become a futuristic candidate in targeting cancer.
Peroxisome Proliferator-Activated Receptors-γ (PPAR-γ), a ligand-activated transcription factor, suggested having anti-inflammatory effects by activating the target genes when bound to the ligand. ...Herein, we examined a conformational analysis of 8708 derivatives of Kaempferol, Quercetin, and Resveratrol, the prime activators of PPAR-γ molecular target by employing molecular docking and dynamic simulation pipeline to screen out potential agonists. The structure-based docking procedure performed by FlexX tool shortlisted high binding affinities of these derivatives of Kaempferol, Quercetin and Resveratrol with the protein receptor with a score of −38.94 kcal/mol (4'-Carboxy-5, 7-Dihydroxyflavone-CDHF), −41.63 kcal/mol (Demethyltorosaflavone D- DMTF) and −31.52 kcal/mol (Resveratrol-O-disulphate- RD) respectively, signifying the selected derivatives forms interactions like H-bond, Aromatic H-Bond, Pi-Pi stacking and salt bridges with PPAR-γ. The PPAR-γ-derivative complex was stabilized by intermolecular hydrogen bonds and stacking interactions. A greater interaction was significantly observed between the binding affinities of derivatives compared to the standards. Based on the root mean square deviation (RMSD) and root mean square fluctuation (RMSF) carried by the means of high-speed molecular dynamics (MD) and simulation of best-docked poses, the ligand, DMTF attained the most favored interaction with PPAR-γ. Thus, it appeared to have high chemical scaffold diversity and may confer high drug-likeness. The binding free energy (ΔG) led us to manifest Quercetin derivative to have a key role for PPAR-γ receptor. The result obtained clearly indicates the exploitation of the promising new drug leads that may further influence in synthesizing and analyzing the development as anti-cancer agonists.
Communicated by Ramaswamy H. Sarma
The recent outbreak of SARS-CoV-2 has quickly become a worldwide pandemic and generated panic threats for both the human population and the global economy. The unavailability of effective vaccines or ...drugs has enforced researchers to hunt for a potential drug to combat this virus. Plant-derived phytocompounds are of applicable interest in the search for novel drugs. Bioflavonoids from Rhus succedanea are already reported to exert antiviral activity against RNA viruses. SARS-CoV-2 Mpro protease plays a vital role in viral replication and therefore can be considered as a promising target for drug development. A computational approach has been employed to search for promising potent bioflavonoids from Rhus succedanea against SARS-CoV-2 Mpro protease. Binding affinities and binding modes between the biflavonoids and Mpro enzyme suggest that all six biflavonoids exhibit possible interaction with the Mpro catalytic site (−19.47 to −27.04 kcal/mol). However, Amentoflavone (−27.04 kcal/mol) and Agathisflavone (−25.87 kcal/mol) interact strongly with the catalytic residues. Molecular dynamic simulations (100 ns) further revealed that these two biflavonoids complexes with the Mpro enzyme are highly stable and are of less conformational fluctuations. Also, the hydrophobic and hydrophilic surface mapping on the Mpro structure as well as biflavonoids were utilized for the further lead optimization process. Altogether, our findings showed that these natural biflavonoids can be utilized as promising SARS-CoV-2 Mpro inhibitors and thus, the computational approach provides an initial footstep towards experimental studies in in vitro and in vivo, which is necessary for the therapeutic development of novel and safe drugs to control SARS-CoV-2.
Communicated by Ramaswamy H. Sarma
Research highlights
Rhus succedanea biflavonoids have antiviral activity.
The molecular interactions and molecular dynamics displayed that all six biflavonoids bound with a good affinity to the same catalytic site of Mpro.
The compound Amentoflavone has a strong binding affinity (−27.0441 kcal/mol) towards Mpro.
The binding site properties of SARS-CoV-2-Mpro can be utilized in a novel discovery and lead optimization of the SARS-CoV-2-Mpro inhibitor.
In this paper, the problem of autonomous optimal absolute orbit keeping for a satellite mission in Low Earth Orbit using electric propulsion is considered. The main peculiarity of the approach is to ...support small satellite missions in which the platform is equipped with a single thruster nozzle that provides acceleration on a single direction at a time. This constraint implies that an attitude maneuver is necessary before or during each thrusting arc to direct the nozzle into the desired direction. In this context, an attitude guidance algorithm specific for the orbit maneuver has been developed. A Model Predictive Control scheme is proposed, where the attitude kinematics are coupled with the orbital dynamics in order to obtain the optimal guidance profiles in terms of satellite state, reference attitude, and thrust magnitude. The proposed control scheme is developed exploiting formation flying techniques where the reference orbit is that of a virtual spacecraft that the main satellite is required to rendezvous with. In addition to the controller design, the closed-loop configuration is presented supported by numerical simulations. The efficacy of the proposed autonomous orbit-keeping approach is shown in several application scenarios.
We fabricated a fourth generation glucose biosensor using CeO2@CuO core shell nano structure (CeCCS NSs). A simple leave extract of Ocimum tenuiflorum was used to prepare different wt% of 0.2, 04, ...0.6, and 0.8 CuO (shell), above 1 wt% of CeO2 (core). The successful formation was confirmed by various characterization techniques like XRD, Uv–Vis, FTIR, SEM and HR-TEM. In the biosensor, 0.4 wt% of CeCCS NSs has shown efficient properties due to its high surface area. The good conductivity and high catalytic activity towards glucose sensing properties were estimated by screen-printed electrode (SPE). The ampherometric studies of CeCCS/SPE modified electrode have been optimized at potential + 0.4 V, showed a sensitivity of 3319.83 μAm M−1 cm−2 within detection limit of 0.019 μM. More significantly, modified electrodes performed excellently against anti-interference and anti-poisoned activity in glucose sample and exhibited promising results for the sustainable improvement for non-enzymatic sensing applications.
•Ocimum tenuiflorum leaf extract were used to prepare Ag@CuO core shell nanostructure.•Structural, optical and morphological properties are studied.•The ACCS/SPE showed a sensitivity of 3319.83 μAmM−1 cm−2.•Bio-mediated route synthesized NSs shows sustainable sensing properties.
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