Harnessing nature's potential: Alpinia galanga methanolic extract mediated green synthesis of silver nanoparticle, characterization and evaluation of anti-neoplastic activity.

With the advent of nanotechnology, the treatment of cancer is changing from a conventional to a nanoparticle-based approach. Thus, developing nanoparticles to treat cancer is an area of immense importance. We prepared silver nanoparticles (AgNPs) from methanolic extract of Alpinia galanga rhizome and characterized them by UV-Vis spectrophotometry, Fourier transform Infrared (FTIR) spectroscopy, Zetasizer, and Transmission electron Microscopy (TEM). UV-Vis spectrophotometry absorption spectrum showed surface plasmon between 400 and 480 nm. FTIR spectrum analysis implies that various phytochemicals/secondary metabolites are involved in the reduction, caping, and stabilization of AgNPs. The Zetasier result suggests that the particles formed are small in size with a low polydispersity index (PDI), suggesting a narrow range of particle distribution. The TEM image suggests that the particles formed are mostly of spherical morphology with nearly 20-25 nm. Further, the selected area electron diffraction (SAED) image showed five electron diffraction rings, suggesting the polycrystalline nature of the particles. The nanoparticles showed high anticancer efficacy against cervical cancer (SiHa) cell lines. The nanostructures showed dose-dependent inhibition with 40% killing observed at 6.25 µg/mL dose. The study showed an eco-friendly and cost-effective approach to the synthesis of AgNPs and provided insight into the development of antioxidant and anticancer agents.

Visible-light promoted catalyst-free (VLCF) multi-component synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids: evaluation of in vitro anticancer activity, molecular docking, MD simulation and DFT studies.

A new and highly efficient visible-light-promoted catalyst free (VLCF) strategy for neat and clean synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids (6a-d) has been introduced. We have performed visible-light triggered 1,3-Dipolar cycloaddition reaction of maleimide (5a-d) with azomethine ylide generated in situ derived from tryptanthrin (3) and L-proline (4) to obtain desired products (6a-d) in good to excellent yield. Authentication and characterization of product was done using various spectroscopic techniques such as IR, 1H NMR, 13C NMR, Mass spectrometry and single crystal XRD analysis. To explain the reaction spontaneity, product stability, reactivity as well as possible mode of the interaction a quantum chemical investigation was performed and depicted through DFT studies. The synthesized compound 6a was also evaluated for anti-proliferative activity against a panel of five cancer cell lines (MCF-7, MDA-MB-231, HeLa, PC-3 and Ishikawa) and normal human embryonic kidney (HEK-293) cell line by using MTT assay. Compound 6a showed very good in vitro anti-proliferative activity (IC50  = 6.58-17.98 µM) against four cancer cell lines and no cytotoxicity against normal HEK-293. In order to evaluate the anticancer potential of compounds 6a-d, molecular docking was performed against wild type and mutant EGFR. The results suggest that all the compounds occupied the active site of both enzymes, with a strong binding energy (-10.2 to -11.5 kcal/mol). These results have been confirmed by molecular dynamics simulation by evaluating root mean square deviation (RMSD) and root mean square fluctuation (RMSF), along with principal component analysis (PCA).Communicated by Ramaswamy H. Sarma.

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma.

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.

Amphotericin B Nano-Assemblies Circumvent Intrinsic Toxicity and Ensure Superior Protection in Experimental Visceral Leishmaniasis with Feeble Toxic Manifestation.

In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani, the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite.

Anticancer effect of zinc oxide nanoparticles prepared by varying entry time of ion carriers against A431 skin cancer cells in vitro.

Although, zinc oxide nanoparticles (ZRTs) as an anti-cancer agent have been the subject of numerous studies, none of the reports has investigated the impact of the reaction entry time of ion-carriers on the preparation of ZRTs. Therefore, we synthesized variants of ZRTs by extending the entry time of NaOH (that acts as a carrier of hydroxyl ions) in the reaction mixture. The anti-proliferative action, morphological changes, reactive oxygen species (ROS) production, and nuclear apoptosis of ZRTs on human A431 skin carcinoma cells were observed. The samples revealed crystallinity and purity by X-ray diffraction (XRD). Scanning electron microscopy (SEM) images of ZRT-1 (5 min ion carrier entry) and ZRT-2 (10 min ion carrier entry) revealed microtubule like morphology. On prolonging the entry time for ion carrier (NaOH) introduction in the reaction mixture, a relative ascent in the aspect ratio was seen. The typical ZnO band with a slight shift in the absorption maxima was evident with UV-visible spectroscopy. Both ZRT-1 and ZRT-2 exhibited non-toxic behavior as evident by RBC lysis assay. Additionally, ZRT-2 showed better anti-cancer potential against A431 cells as seen by MTT assay, ROS generation and chromatin condensation analyses. At 25 µM of ZRT-2, 5.56% cells were viable in MTT test, ROS production was enhanced to 166.71%, while 33.0% of apoptotic cells were observed. The IC50 for ZRT-2 was slightly lower (6 µM) than that for ZRT-1 (8 µM) against A431 cells. In conclusion, this paper presents a modest, economical procedure to generate ZRT nano-structures exhibiting strong cytotoxicity against the A431 cell line, indicating that ZRTs may have application in combating cancer.

Prevalence of rheumatoid arthritis and diagnostic validity of a prediction score, in patients visiting orthropedic clinics in the Madinah region of Saudi Arabia: a retrospective cross-sectional study.

Introduction: In Saudi Arabia, the epidemiology of rheumatoid arthritis (RA) is not well studied and is marked by inconsistencies in clinical diagnosis. Therefore, in this study, we explored the prevalence, clinical characteristics, and diagnostic validity of a prediction score based upon disease markers in orthropedic clinics' patients in the Madinah region of Saudi Arabia. Method: The clinical data for this retrospective cross-sectional study were retrieved from the database registry of orthopedic clinics in selected hospitals of the Medinah province of Saudi Arabia. Sociodemographic features, disease markers and the clinical characteristics were collected for a period of 6 months, from December 1, 2020, to May 31, 2021. The prediction score was generated from the sum of disease markers, coded as dichotomous variables. Results: The total sample size of our study was 401. The prevalence of RA in the study subjects (n = 401) was 14.46% (n = 58). Among RA patients, the majority were females (60.3%). Painful joints (69%) and swollen joints (51.7%) were the most common clinical complaints among RA patients. RA patients suffered from arthritis (51.7%) and experienced fatigue (46.6%), weight loss (44.8%), and loss of appetite (41.4%). Diabetes (55.2%) was the most common comorbidity in the RA patients. The sensitivity and specificity of the prediction score at the criterion score of 2.5 were 67.3% and 63.0%, respectively. The area under the curve was 0.69 (95% CI [0.62-0.76]). Conclusion: There was a moderately high prevalence of RA in patients visiting the orthropedic clinics of the selected hospitals of Madinah region of Saudi Arabia. The diagnostic validity of the prediction score, though promising, was slightly lower than the acceptable range.

Effect of Date Palm (Phoenix dactylifera) Phytochemicals on Aß1-40 Amyloid Formation: An in-silico Analysis.

Alzheimer's disease (AD) is a neurodegenerative disease and the most prevalent form of dementia. The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of AD. It has been suggested that date palm, a plant rich in phenolic compounds and flavonoids, can provide an alternative treatment to fight memory loss and cognitive dysfunction due to its potent antioxidant activity. Thus, we studied the effect of flavonoids present in date palm on Aß1-40 amyloid formation using molecular docking and molecular dynamics simulation. AutoDock. Myricetin was used as a positive control drug. The flavonoids Diosmetin, Luteolin, and Rutin were found to be potent inhibitors of aggregation (docking energies ≤ -8.05 kcal mol-1) targeting Aß1-40 fibrils (both 2LMO and 6TI5), simultaneously. Further screening by physicochemical properties and drug-likeness analysis suggested that all flavonoids except Rutin followed Lipinski's rule of five. Rutin was, thus, taken as a negative control (due to its violation of Lipinski's rule) to compare its dynamics with Diosmetin. Diosmetin exhibited the highest positive scores for drug likeness. Since Luteolin exhibited moderate drug-likeness and better absorption properties, it was also included in molecular dynamics simulation. Molecular dynamics of shortlisted compounds (Rutin, Diosmetin, and Luteolin) were performed for 200 ns, and the results were analyzed by monitoring root mean square deviations (RMSD), root mean square fluctuation (RMSF) analysis, the radius of gyration (Rg), and solvent accessible surface area (SASA). The results proved the formation of a stable protein-compound complex. Based on binding energies and non-bonded interactions, Rutin and Luteolin emerged as better lead molecules than Diosmetin. However, high MW (610.5), lowest absorption rate (16.04%), and more than one violation of Lipinski's rule make Rutin a less likely candidate as an anti-amyloidogenic agent. Moreover, among non-violators of Lipinski's rule, Diosmetin exhibited a greater absorption rate than Luteolin as well as the highest positive scores for drug-likeness. Thus, we can conclude that Diosmetin and Luteolin may serve as a scaffold for the design of better inhibitors with higher affinities toward the target proteins. However, these results warrant in-vitro and in-vivo validation before practical use.

ZnO Nano-swirlings for Azo Dye AR183 photocatalytic degradation and antimycotic activity.

The sol-gel technique was used to fabricate ZnO Nano-swirlings (ZNsw) at a predetermined agitation rate (of >> 1900 rpm), with around 21.94 gm of zinc acetate dihydrate and 0.2 g cetyltrimethylammoniumbromide (CTAB) and a cationic surfactant (drop-wise). The impact of the predetermined agitation condition on the molecular size and morphology of ZNsw is examined, and the outcomes are dissected by useful characterization tools and techniques viz. XRD, SEM embedded with EDS, TEM, FT-IR and UV-visible. The SEM and TEM results suggest that the product formed into a big cluster of adequate ZNsw, containing a significant quantity of folded long thread-lengths. Each group indicated a fair amount of the volume of these lengths. The photocatalytic process of ZNsw was carried out as a result of the irradiation time due to the deterioration of Azo Dye AR183, resulting in approximately 79 percent dye discoloration following an 80-min UV light irradiation in the presence of ZNsw. Additionally, the synthesized ZNsw was tested for antagonistic activity, and the growth hindrance of two plant pathogenic fungal strains found. Per cent inhibition in growth of Rhizoctonia solani and Alternaria alternata were observed in response to ZNsw.

Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites of Bauhinia variegata to Treat Alzheimer's Disease.

Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer's disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein-ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of -12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1-quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer's disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.

Soyasapogenol-B as a Potential Multitarget Therapeutic Agent for Neurodegenerative Disorders: Molecular Docking and Dynamics Study.

Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to neurodegenerative disorders such as Alzheimer's disease. Initially, abrineurin natural inducers were screened using physicochemical properties and toxicity assessment. Out of five screened compounds, a pentacyclic triterpenoid, i.e., Soyasapogenol B appeared to be the most promising after molecular docking and simulation analysis. Soyasapogenol B showed low TPSA (60.69), high absorption (82.6%), no Lipinski rule violation, and no toxicity. Docking interaction analysis revealed that Soyasapogenol B bound effectively to all of the targeted proteins (AChE, BuChE MAO-A, MAO-B, GSK3ß, and NMDA), in contrast to other screened abrineurin natural inducers and inhibitors. Importantly, Soyasapogenol B bound to active site residues of the targeted proteins in a similar pattern to the native ligand inhibitor. Further, 100 ns molecular dynamics simulations analysis showed that Soyasapogenol B formed stable complexes against all of the targeted proteins. RMSD analysis showed that the Soyasapogenol B-protein complex exhibited average RMSD values of 1.94 Å, 2.11 Å, 5.07 Å, 2.56 Å, 3.83 Å and 4.07 Å. Furthermore, the RMSF analysis and secondary structure analysis also indicated the stability of the Soyasapogenol B-protein complexes.

Isolation and optimization of extracellular PHB depolymerase producer Aeromonas caviae Kuk1-(34) for sustainable solid waste management of biodegradable polymers.

Bioplastics, synthesized by several microbes, accumulates inside cells under stress conditions as a storage material. Several microbial enzymes play a crucial role in their degradation. This research was carried to test the biodegradability of poly-ß-hydroxybutyrate (PHB) utilizing PHB depolymerase, produced by bacteria isolated from sewage waste soil samples. Potent PHB degrader was screened based on the highest zone of hydrolysis followed by PHB depolymerase activity. Soil burial method was employed to check their degradation ability at different incubation periods of 15, 30, and 45 days at 37±2°C, pH 7.0 at 60% moisture with 1% microbial inoculum of Aeromonas caviae Kuk1-(34) (MN414252). Without optimized conditions, 85.76% of the total weight of the PHB film was degraded after 45 days. This degradation was confirmed with Fourier-transform infrared spectroscopy (FTIR) and Scanning electron microscope (SEM) analysis. The presence of bacterial colonies on the surface of the degraded film, along with crest, holes, surface erosion, and roughness, were visible. Media optimization was carried out in statistical mode using Plackett Burman (PB) and Central Composite Design (CCD) of Response Surface Methodology (RSM) by considering ten different factors. Analysis of Variance (ANOVA), Pareto chart, response surface plots, and F-value of 3.82 implies that the above statistical model was significant. The best production of PHB depolymerase enzyme (14.98 U/mL) was observed when strain Kuk1-(34) was grown in a media containing 0.1% PHB, K2HPO4 (1.6 gm/L) at 27 ℃ for seven days. Exploiting these statistically optimized conditions, the culture was found to be a suitable candidate for the management of solid waste, where 94.4% of the total weight of the PHB film was degraded after 45 days of incubation.

Anticancer potential of Phoenix dactylifera L. seed extract in human cancer cells and pro-apoptotic effects mediated through caspase-3 dependent pathway in human breast cancer MDA-MB-231 cells: an in vitro and in silico investigation.

BACKGROUND: Phoenix dactylifera L. has a diverse set of pharmacological properties due to its distinct phytochemical profile. The purpose of this study was to investigate the anticancer potential of Phoenix dactylifera seed extract (PDSE) in human breast cancer MDA-MB-231 and MCF-7 cells, as well as liver cancer HepG2 cells, and to investigate the anticancer efficacy in triple-negative MDA-MB-231 cells, followed by in silico validation of the molecular interaction between active components of PDSE and caspase-3, an apoptosis executioner protein . METHODS: In this study, human cancer cell lines were cultured and subsequently treated with 10 to 100 µg/mL of PDSE. MTT test was performed to determine the cell viability, MMP was measured using fluorescent probe JC-1, nuclear condensation was determined by Hoechst 33258 dye, Annexin V-FITC & PI staining and cell cycle analysis were evaluated through flow cytometer, and apoptotic markers were detected using western blotting. The bioactive agents in PDSE were identified using high-performance liquid chromatography (HPLC) analysis. The binding affinity was validated using molecular docking tools AutoDock Vina and iGEMDOCK v2.1. RESULTS: Cell viability data indicated that PDSE inhibited cell proliferation in both breast cancer cells and liver cancer cells. MDA-MB-231 cells showed maximum growth inhibition with an IC50 value of 85.86 µg/mL for PDSE. However, PDSE did not show any significant toxicity against the normal Vero cell line. PDSE induced MMP loss and formation of apoptotic bodies, enhanced late apoptosis at high doses and arrested cells in the S phase of cell cycle. PDSE activated the enzymatic activity of cleaved caspase-3 and caused the cleavage of poly-ADB ribose polymerase (PARP) protein. PDSE upregulated pro-apoptotic Bax protein markedly but  no significant effect on tumor suppressor protein p53, while it downregulated the anti-apoptotic Bcl-2 protein expression. HPLC analysis showed the presence of rutin and quercetin bioactive flavonols in ethanolic extract of PDS. Interestingly, both active components revealed a strong binding interaction with amino acid residues of caspase-3 (PDB ID: 2XYP; Hetero 4-mer - A2B2) protein. CONCLUSION: PDS could serve as a potential medicinal source for apoptotic cell death in human breast cancer cells and, thus, could be used as a promising and crucial candidate in anticancer drug development. This study warrants further in vivo research, followed by clinical investigation.

Crosstalk between SARS-CoV-2 Infection and Type II Diabetes.

Since the outbreak of coronavirus disease (COVID-19) in Wuhan, China, triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) in late November 2019, spreading to more than 200 countries of the world, the ensuing pandemic to an enormous loss of lives, mainly the older population with comorbidities, like diabetes, cardiovascular disease, chronic obstructive pulmonary disease, obesity, and hypertension. Amongst these immune-debilitating diseases, SARS-CoV-2 infection is the most common in patients with diabetes due to the absence of a normal active immune system to fight the COVID-19. Recovery of patients having a history of diabetes from COVID-19 encounters several complications, and their management becomes cumbersome. For control of coronavirus, antiviral medications, glucose-lowering agents, and steroids have been carefully evaluated. In the present review, we discuss the crosstalk between SARS-CoV-2 infection and patients with a history of diabetes. We mainly emphasize the molecular factors that are involved in diabetic individuals recently infected by SARS-CoV-2 and developed COVID-19 disease. Lastly, we examine the medications available for the long-term management of diabetic patients with SARS-CoV-2 infection.

Bioprospecting of the novel isolate Microbacterium proteolyticum LA2(R) from the rhizosphere of Rauwolfia serpentina.

The study aimed to assess the proficiency of secondary metabolites (SMs) synthesized by actinobacteria isolated from the rhizospheric soil of Rauwolfia serpentina for its antimicrobial and anti-biofilm activity. After morphological and biochemical identification of actinobacteria, primary and secondary screening was done for specific metabolite production. The secondary metabolites were then tested for their antioxidant, antibacterial, and antibiofilm potential. Out of 29 bacterial colonies isolated, only one emerged as a novel isolate, Microbacterium LA2(R). Partial 16S rRNA gene sequence of the isolate LA2(R) was deposited in NCBI GenBank with accession number MN560041. The highest antioxidant capacity of the methanolic extract the novel isolate was found to be 474.183 µL AAE/mL and 319.037 µL AAE/mL by DPPH assay and ABTS assay respectively; three folds higher than the control. These results were further supported by the high total phenolic (194.95 gallic acid equivalents/mL) and flavonoid contents (332.79 µL quercetin equivalents/mL) of the methanolic extract. GC-MS analysis revealed the abundance of antibacterial compounds; where, n-Hexadecanoic acid was found to be the major compound present with a peak of 14 min retention time (RT) and 95% similarity index. MIC value of the metabolite was noted to be around 132.28 ± 84.48 µg/mL. The IC50 value was found to be 74.37, 71.33, 66.28 and 84.48 µg/mL against Escherichia coli, Staphylococcus aureus, Klebsiella pneumonia, and Salmonella abony, respectively. Treatment with IC50 of the extract decreased the biofilm formation up to 70%-80% against pathogenic strains viz. Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Salmonella abony. These significant activities of Microbacterium sp. LA2(R) suggests that it could be utilized for antibiotic production for human welfare and in various important industrial applications.

Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS-CoV-2: An integrative phytochemical and computational approach.

Therapeutic drugs based on natural products for the treatment of SARS-CoV-2 are currently unavailable. This study was conducted to develop an anti-SARS-CoV-2 herbal medicine to face the urgent need for COVID-19 treatment. The bioactive components from ethanolic extract of Moringa oleifera fruits (MOFs) were determined by gas chromatography-mass spectroscopy (GC-MS). Molecular-docking analyses elucidated the binding effects of identified phytocomponents against SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and human ACE2 receptor (PDB ID: 1R42) through the Glide module of Maestro software. GC-MS analysis unveiled the presence of 33 phytocomponents. Eighteen phytocomponents exhibited good binding affinity toward ACE2 receptor, and thirteen phytocomponents had a high affinity with spike glycoprotein. This finding suggests that the top 11 hits (Docking score ≥ -3.0 kcal/mol) could inhibit SARS-CoV-2 propagation. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. However, further studies are needed to validate their effects and mechanisms of action. PRACTICAL APPLICATIONS: Moringa oleifera (MO) also called "drumstick tree" has been used as an alternative food source to combat malnutrition and may act as an immune booster. GC-MS analysis unveiled that ethanolic extract of Moringa oleifera fruits (MOFs) possessed 33 active components of pyridine, aromatic fatty acid, oleic acid, tocopherol, methyl ester, diterpene alcohol, triterpene and fatty acid ester and their derivatives, which have various pharmacological and medicinal values. Virtual screening study of phytocomponents of MOF with human ACE2 receptor and SARS-CoV-2 spike glycoprotein exhibited good binding affinity. Based on molecular docking, the top 11 hits (Docking score ≥-3.0 kcal/mol) might serve as potential lead molecules in antiviral drug development. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. Thus, MOF might be used as a valuable source for antiviral drug development to combat COVID-19, an ongoing pandemic.

Multifaceted Pharmacological Potentials of Curcumin, Genistein, and Tanshinone IIA through Proteomic Approaches: An In-Depth Review.

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future.

Aminoglycosides as potential inhibitors of SARS-CoV-2 main protease: an in silico drug repurposing study on FDA-approved antiviral and anti-infection agents.

BACKGROUND: The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic. METHODS: The main protease (Mpro) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation. RESULTS: Out of 1397 potential drugs, 157 showed considerable affinity toward Mpro. After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies -10.629 to -11.776kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (-73.800kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against Mpro. All aminoglycosides were bound to the substrate-binding site of Mpro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of Mpro. MD simulations of the Amikacin-Mpro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions. CONCLUSION: Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent.

Antiproliferative Activity of Cissus quadrangularis L. Extract Against Human Cervical Cancer Cells: In Vitro and In Silico Analysis.

BACKGROUND: Cervical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents. OBJECTIVE: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3. METHODS: Cell viability was analyzed in HeLa cells at different concentrations (25-300 µg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico, structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK. RESULTS: Cell viability of HeLa cells was reduced significantly (p < 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski's Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. CONCLUSION: This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer.

Anti-quorum Sensing and Anti-biofilm Activity of Zinc Oxide Nanospikes.

This study evaluates the impact of two separate incubation periods (4 and 6 weeks) on the morphology of sol-gel-fabricated ZnO nanospikes (ZNs), that is, ZN1 and ZN2, respectively. We further analyzed the inhibitory effects of ZN1 and ZN2 on quorum sensing (QS) and biofilm formation in Pseudomonas aeruginosa (PAO1) and Chromobacterium violaceum (strains 12472 and CVO26). The size of the synthesized ZNs was in the range of 40-130 nm, and finer nanoparticles were synthesized after an incubation period of 6 weeks. Treatment with ZNs decreased the production of violacein in the pathogen without affecting the bacterial growth, which indicated that ZNs inhibited the QS signaling regulated by N-acyl homoserine lactone. ZN2 had a higher inhibitory action on the virulence factor productivity than ZN1. Furthermore, ZN2-treated cells displayed a substantial decrease in azocasein-degrading protease activity (80%), elastase activity (83%), and pyocyanin production (85%) relative to untreated P. aeruginosa PAO1 cells. Treatment with ZN2 decreased swarming motility and exopolysaccharide production by 89 and 85%, respectively. ZN2 was effective against both the las & pqs systems of P. aeruginosa and exhibited broad-spectrum activity. Additionally, ZN2 was more efficient in inhibiting the biofilm formation at the attachment stage than ZN1. These findings revealed that in P. aeruginosa, ZN2 demonstrated inhibitory effects on QS as well as on the development of biofilms. Thus, ZN2 can be potentially used to treat drug-resistant P. aeruginosa infections.

Current analytical methods for porcine identification in meat and meat products.

Authentication of meat products is critical in the food industry. Meat adulteration may lead to religious apprehensions, financial gain and food-toxicities such as meat allergies. Thus, empirical validation of the quality and constituents of meat is paramount. Various analytical methods often based on protein or DNA measurements are utilized to identify meat species. Protein-based methods, including electrophoretic and immunological techniques, are at times unsuitable for discriminating closely related species. Most of these methods have been replaced by more accurate and sensitive detection methods, such as DNA-based techniques. Emerging technologies like DNA barcoding and mass spectrometry are still in their infancy when it comes to their utilization in meat detection. Gold nanobiosensors have shown some promise in this regard. However, its applicability in small scale industries is distant. This article comprehensively reviews the recent developments in the field of analytical methods used for porcine identification.