A versatile sensor capable of ratiometric fluorescence detection of trace water and turn-on detection of Cu2+ modulating the binding interaction of a Cu(II) complex with BSA and DNA complemented by docking studies.

A fluorescent molecule, pyridine-coupled bis-anthracene (PBA), has been developed for the selective fluorescence turn-on detection of Cu2+. Interestingly, the ligand PBA also exhibited a red-shifted ratiometric fluorescence response in the presence of water. Thus, a ratiometric water sensor has been utilized as a selective fluorescence turn-on sensor for Cu2+, achieving a 10-fold enhancement in the fluorescence and quantum yield at 446 nm, with a lower detection limit of 0.358 µM and a binding constant of 1.3 × 106 M-1. For practical applications, sensor PBA can be used to detect Cu2+ in various types of soils like clay soil, field soil and sand. The interaction of the PBA-Cu(II) complex with transport proteins like bovine serum albumin (BSA) and ct-DNA has been investigated through fluorescence titration experiments. Additionally, the structural optimization of PBA and the PBA-Cu(II) complex has been demonstrated by DFT, and the interaction of the PBA-Cu(II) complex with BSA and ct-DNA has been analyzed using theoretical docking studies.

A top-down approach for studying the in-silico effect of the novel phytocompound tribulusamide B on the inhibition of Nipah virus transmission through targeting fusion glycoprotein and matrix protein.

The proteins of Nipah virus ascribe to its lifecycle and are crucial to infections caused by the virus. In the absence of approved therapeutics, these proteins can be considered as drug targets. This study examined the potential of fifty-three (53) natural compounds to inhibit Nipah virus fusion glycoprotein (NiV F) and matrix protein (NiV M) in silico. The molecular docking experiment, supported by the principal component analysis (PCA), showed that out of all the phytochemicals considered, Tribulusamide B had the highest inhibitory potential against the target proteins NiV F and NiV M (-9.21 and -8.66 kcal mol-1, respectively), when compared to the control drug, Ribavirin (-7.01 and -6.52 kcal mol-1, respectively). Furthermore, it was found that Tribulusamide B pharmacophores, namely, hydrogen donors, acceptors, aromatic and hydrophobic groups, contributed towards the effective residual interactions with the target proteins. The molecular dynamic simulation further validated the results of the docking studies and concluded that Tribulusamide B formed a stable complex with the target proteins. The data obtained from MM-PBSA study further explained that the phytochemical could strongly bind with NiV F (-31.26 kJ mol-1) and NiV M (-40.26 kJ mol-1) proteins in comparison with the control drug Ribavirin (-13.12 and -13.94 kJ mol-1, respectively). Finally, the results indicated that Tribulusamide B, a common inhibitor effective against multiple proteins, can be considered a potential therapeutic entity in treating the Nipah virus infection.

Citrus Medica-derived Fluorescent Carbon Dots for the Imaging of Vigna Radiate Root Cells.

Bio-imaging is a crucial tool for researchers in the fields of cell biology and developmental biomedical sector. Among the various available imaging techniques, fluorescence based imaging stands out due to its high sensitivity and specificity. However, traditional fluorescent materials used in biological imaging often suffer from issues such as photostability and biocompatibility. Moreover, plant tissues contain compounds that cause autofluorescence and light scattering, which can hinder fluorescence microscopy effectiveness. This study explores the development of fluorescent carbon dots (Cm-CDs) synthesized from Citrus medica fruit extract for the fluorescence imaging of Vigna radiata root cells. The successful synthesis of CDs with an average size of 6.7 nm is confirmed by Transmission Electron Microscopy (TEM). The X-ray diffraction (XRD) analysis and raman spectroscopy indicated that the obtained CDs are amorphous in nature. The presence of various functional groups on the surface of CDs were identified by Fourier transform infrared (FTIR) spectra. The optical characteristics of Cm-CDs were studied by UV-Visible spectroscopy and photoluminescence spectroscopy. Cm-CDs demonstrated strong excitation-dependent fluorescence, good solubility, and effective penetration in to the Vigna radiata root cells with multicolor luminescence, and addressed autofluorescence issues. Additionally, a comparative analysis determined the optimal concentration for high-resolution, multi-color root cell imaging, with Cm-CD2 (2.5 mg/ml) exhibiting the highest photoluminescence (PL) intensity. These findings highlight the potential of Cm-CDs in enhancing direct endocytosis and overcoming autofluorescence in plant cell imaging, offering promising advancements for cell biology research.

Homoharringtonine: updated insights into its efficacy in hematological malignancies, diverse cancers and other biomedical applications.

HHT has emerged as a notable compound in the realm of cancer treatment, particularly for hematological malignancies. Its multifaceted pharmacological properties extend beyond traditional applications, warranting an extensive review of its mechanisms and efficacy. This review aims to synthesize comprehensive insights into the efficacy of HHT in treating hematological malignancies, diverse cancers, and other biomedical applications. It focuses on elucidating the molecular mechanisms, therapeutic potential, and broader applications of HHT. A comprehensive search for peer-reviewed papers was conducted across various academic databases, including ScienceDirect, Web of Science, Scopus, American Chemical Society, Google Scholar, PubMed/MedLine, and Wiley. The review highlights HHT's diverse mechanisms of action, ranging from its role in leukemia treatment to its emerging applications in managing other cancers and various biomedical conditions. It underscores HHT's influence on cellular processes, its efficacy in clinical settings, and its potential to alter pathological pathways. HHT demonstrates significant promise in treating various hematological malignancies and cancers, offering a multifaceted approach to disease management. Its ability to impact various physiological pathways opens new avenues for therapeutic applications. This review provides a consolidated foundation for future research and clinical applications of HHT in diverse medical fields.

Development of a fluorescent scaffold by utilizing quercetin template for selective detection of Hg2+: Experimental and theoretical studies along with live cell imaging.

Quercetin is an important antioxidant with high bioactivity and it has been used as SARS-CoV-2 inhibitor significantly. Quercetin, one of the most abundant flavonoids in nature, has been in the spot of numerous experimental and theoretical studies in the past decade due to its great biological and medicinal importance. But there have been limited instances of employing quercetin and its derivatives as a fluorescent framework for specific detection of various cations and anions in the chemosensing field. Therefore, we have developed a novel chemosensor based on quercetin coupled benzyl ethers (QBE) for selective detection of Hg2+ with "naked-eye" colorimetric and "turn-on" fluorometric response. Initially QBE itself exhibited very weak fluorescence with low quantum yield (Φ = 0.009) due to operating photoinduced electron transfer (PET) and inhibition of excited state intramolecular proton transfer (ESIPT) as well as intramolecular charge transfer (ICT) within the molecule. But in presence of Hg2+, QBE showed a sharp increase in fluorescence intensity by 18-fold at wavelength 444 nm with high quantum yield (Φ = 0.159) for the chelation-enhanced fluorescence (CHEF) with coordination of Hg2+, which hampers PET within the molecule. The strong binding affinity of QBE towards Hg2+ has been proved by lower detection limit at 8.47 µM and high binding constant value as 2 × 104 M-1. The binding mechanism has been verified by DFT study, Cyclic voltammograms and Jobs plot analysis. For the practical application, the binding selectivity of QBE with Hg2+ has been capitalized in physiological medium to detect intracellular Hg2+ levels in living plant tissue by using green gram seeds. Thus, employing QBE as a fluorescent chemosensor for the specific identification of Hg2+ will pave the way for a novel approach to simplifying the creation of various chemosensors based on quercetin backbone for the precise detection of various biologically significant analytes.

Unravelling Post-harvest Ripening Metabolomics of a New White Variety Guava Fruit (Cv Arka Mridula) with Special Emphasis on Phenolics and Corresponding Antioxidants.

The phenolic, antioxidant and metabolic profiling of a new white variety guava fruit Arka Mridula (AM) was performed during its storage at the room temperature (28 ± 2 °C). The comparative profiles were generated at three ripening stages (pre-ripe, ripe and over-ripe) of the fruit. Generally, a steady decrease of the phenolic and antioxidant content from the pre-ripe to the ripe stage and a subsequent increase from the ripe to over-ripe stage was observed. Further, a powerful correlation between the phenolic content and antioxidant principles was noted through the principal component analysis. We could identify 53  compounds for the hydro-methanolic fruit extract through LC and GC-MS aided metabolic analysis, and the identified compounds were dominated by phenolics (~ 44%). The statistical analysis revealed that phytochemicals catechin, myricitrin, myricetin, kaempferol glycosides and n-hexadecanoic acid contributed significantly towards the ripening process of AM, during the storage. The present study is expected to provide important insight into the ripening biochemistry of AM. Subsequently, it may help in the future development of metabolically stable guava cultivars with extended post-harvest shelf life.

Viscosity-sensitive and AIE-active bimodal fluorescent probe for the selective detection of OCl- and Cu2+: a dual sensing approach via DFT and biological studies using green gram seeds.

A novel dual-mode viscosity-sensitive and AIE-active fluorescent chemosensor based on the naphthalene coupled pyrene (NCP) moiety was designed and synthesized for the selective detection of OCl- and Cu2+. In non-viscous media, NCP exhibited weak fluorescence; however, with an increase in viscosity using various proportions of glycerol, the fluorescence intensity was enhanced to 461 nm with a 6-fold increase in fluorescence quantum yields, which could be utilized for the quantitative determination of viscosity. Interestingly, NCP exhibited novel AIE characteristics in terms of size and growth in H2O-CH3CN mixtures with high water contents and different volume percentage of water, which was investigated using fluorescence, DLS study and SEM analysis. Interestingly, this probe can also be effectively employed as a dual-mode fluorescent probe for light up fluorescent detection of OCl- and Cu2+ at different emission wavelengths of 439 nm and 457 nm via chemodosimetric and chelation pathways, respectively. The fast-sensing ability of NCP towards OCl- was shown by a low detection limit of 0.546 µM and the binding affinity of NCP with Cu2+ was proved by a low detection limit of 3.97 µM and a high binding constant of 1.66 × 103 M-1. The sensing mechanism of NCP towards OCl- and Cu2+ was verified by UV-vis spectroscopy, fluorescence analysis, 1H-NMR analysis, mass spectroscopy, DFT study and Job plot analysis. For practical applications, the binding of NCP with OCl- and Cu2+ was determined using a dipstick method and a cell imaging study in a physiological medium using green gram seeds.

Anticancer activity and other biomedical properties of ß-sitosterol: Bridging phytochemistry and current pharmacological evidence for future translational approaches.

Sterols, including ß-sitosterol, are essential components of cellular membranes in both plant and animal cells. Despite being a major phytosterol in various plant materials, comprehensive scientific knowledge regarding the properties of ß-sitosterol and its potential applications is essential for scholarly pursuits and utilization purposes. ß-sitosterol shares similar chemical characteristics with cholesterol and exhibits several pharmacological activities without major toxicity. This study aims to bridge the gap between phytochemistry and current pharmacological evidence of ß-sitosterol, focusing on its anticancer activity and other biomedical properties. The goal is to provide a comprehensive understanding of ß-sitosterol's potential for future translational approaches. A thorough examination of the literature was conducted to gather relevant information on the biological properties of ß-sitosterol, particularly its anticancer therapeutic potential. Various databases were searched, including PubMed/MedLine, Scopus, Google Scholar, and Web of Science using appropriate keywords. Studies investigating the effects of ß-sitosterol on different types of cancer were analyzed, focusing on mechanisms of action, pharmacological screening, and chemosensitizing properties. Modern pharmacological screening studies have revealed the potential anticancer therapeutic properties of ß-sitosterol against various types of cancer, including leukemia, lung, stomach, breast, colon, ovarian, and prostate cancer. ß-sitosterol has demonstrated chemosensitizing effects on cancer cells, interfering with multiple cell signaling pathways involved in proliferation, cell cycle arrest, apoptosis, survival, metastasis invasion, angiogenesis, and inflammation. Structural derivatives of ß-sitosterol have also shown anti-cancer effects. However, research in the field of drug delivery and the detailed mode of action of ß-sitosterol-mediated anticancer activities remains limited. ß-sitosterol, as a non-toxic compound with significant pharmacological potential, exhibits promising anticancer effects against various cancer types. Despite being relatively less potent than conventional cancer chemotherapeutics, ß-sitosterol holds potential as a safe and effective nutraceutical against cancer. Further comprehensive studies are recommended to explore the biological properties of ß-sitosterol, including its mode of action, and develop novel formulations for its potential use in cancer treatment. This review provides a foundation for future investigations and highlights the need for further research on ß-sitosterol as a potent superfood in combating cancer.

Exploring the potential of Andrographis paniculata for developing novel HDAC inhibitors: an in silico approach.

Cancer is one of the dreaded diseases of the twentieth century, emerging the major global causes of human morbidity. Cancer research in the last 15 years has provided unprecedented information on the role of epigenetics in cancer initiation and progression. Histone deacetylases (HDACs) are recognized as important epigenetic markers in cancer, whose overexpression leads to increased metastasis and angiogenesis. In the current study, thirty-four (34) compounds from Andrographis paniculata were screened for the identification of potential candidate drugs, targeting three Class I HDACs (Histone deacetylases), namely HDAC1 (PDB id 5ICN), HDAC3 (PDB id 4A69) and HDAC8 (PDB id 5FCW) through computer-assisted drug discovery study. Results showed that some of the phytochemicals chosen for this study exhibited significant drug-like properties. In silico molecular docking study further revealed that out of 34 compounds, the flavonoid Andrographidine E had the highest binding affinities towards HDAC1 (-9.261 Kcal mol-1) and 3 (-9.554 Kcal mol-1) when compared with the control drug Givinostat (-8.789 and -9.448 Kcal mol-1). The diterpenoid Andrographiside displayed the highest binding affinity (-9.588 Kcal mol-1) to HDAC8 compared to Givinostat (-8.947 Kcal mol-1). Statistical analysis using Principal Component Analysis tool revealed that all 34 phytocompounds could be clustered in four statistical groups. Most of them showed high or comparable inhibitory potentials towards HDAC target protein. Finally, the stability of top-ranked complexes (Andrographidine E-HDAC1 and HDAC3; Andrographiside-HDAC8) at the physiological condition was validated by Molecular Dynamic Simulation and MM-PBSA study.Communicated by Ramaswamy H. Sarma.

Evaluation of therapeutic potentials of selected phytochemicals against Nipah virus, a multi-dimensional in silico study.

The current study attempted to evaluate the potential of fifty-three (53) natural compounds as Nipah virus attachment glycoprotein (NiV G) inhibitors through in silico molecular docking study. Pharmacophore alignment of the four (4) selected compounds (Naringin, Mulberrofuran B, Rutin and Quercetin 3-galactoside) through Principal Component Analysis (PCA) revealed that common pharmacophores, namely four H bond acceptors, one H bond donor and two aromatic groups were responsible for the residual interaction with the target protein. Out of these four compounds, Naringin was found to have the highest inhibitory potential ( - 9.19 kcal mol-1) against the target protein NiV G, when compared to the control drug, Ribavirin ( - 6.95 kcal mol-1). The molecular dynamic simulation revealed that Naringin could make a stable complex with the target protein in the near-native physiological condition. Finally, MM-PBSA (Molecular Mechanics-Poisson-Boltzmann Solvent-Accessible Surface Area) analysis in agreement with our molecular docking result, showed that Naringin ( - 218.664 kJ mol-1) could strongly bind with the target protein NiV G than the control drug Ribavirin ( - 83.812 kJ mol-1). Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03595-y.

Phytochemical Composition, Bioactive Compounds, and Antioxidant Properties of Different Parts of Andrographis macrobotrys Nees.

Andrographis macrobotrys Nees is an ethnomedicinal plant belonging to the family Acanthaceae, distributed in the moist deciduous and semi-evergreen forests of the southern Western Ghats of India. The objective of this research was to determine the phytochemical composition and bioactive chemical components using gas chromatography and mass spectrometry (GC-MS) and to check the antioxidant potential of the plant part extracts. A. macrobotrys roots, stems, and leaves were obtained from the species' natural habitat in the Western Ghats, India. The bioactive compounds were extracted using a Soxhlet extractor at 55-60 °C for 8 h in methanol. Identification analysis of A. macrobotrys bioactive compound was performed using GC-MS. Quantitative estimation of phytochemicals was carried out, and the antioxidant capacity of the plant extracts was determined by 2,2'-diphenyl-1-picrylhydrazyl radical scavenging (DPPH) and ferric reducing assays (FRAP). A. macrobotrys has a higher concentration of phenolics in its stem extract than in its root or leaf extracts (124.28 mg and 73.01 mg, respectively), according to spectrophotometric measurements. GC-MS analysis revealed the presence of phytochemicals such as azulene, 2,4-di-tert-butylphenol, benzoic acid, 4-ethoxy-ethyl ester, eicosane, 3-heptadecanol, isopropyl myristate, hexadecanoic acid methyl ester, hexadecanoic acid, 1-butyl-cyclohexanol, 9,12-octadecadienoic acid, alpha-monostearin, and 5-hydroxy-7,8-dimethoxyflavone belonging to various classes of flavonoids, terpenoids, phenolics, fatty acids, and aromatic compounds. Significant bioactive phytochemicals include 2,4-di-tert-butylphenol, 2-methoxy-4-vinylphenol, 5-hydroxy-7,8-dimethoxyflavone, azulene, salvigenin, squalene, and tetrapentacontane. In addition, the antioxidant capability of each of the three extracts was assessed. The stem extract demonstrated impressive DPPH scavenging and ferric reduction activities, with EC50 values of 79 mg/mL and 0.537 ± 0.02 OD at 0.2 mg/mL, respectively. The results demonstrated the importance of A. macrobotrys as a source of medicine and antioxidants.

Optimized production of keratinolytic proteases from Bacillus tropicus LS27 and its application as a sustainable alternative for dehairing, destaining and metal recovery.

The present study describes the isolation and characterization of Bacillus tropicus LS27 capable of keratinolytic protease production from Russell Market, Shivajinagar, Bangalore, Karnataka, with its diverse application. The ability of this strain to hydrolyze chicken feathers and skim milk was used to assess its keratinolytic and proteolytic properties. The strain identification was done using biochemical and molecular characterization using the 16S rRNA sequencing method. Further a sequential and systematic optimization of the factors affecting the keratinase production was done by initially sorting out the most influential factors (NaCl concentration, pH, inoculum level and incubation period in this study) through one factor at a time approach followed by central composite design based response surface methodology to enhance the keratinase production. Under optimized levels of NaCl (0.55 g/L), pH (7.35), inoculum level (5%) and incubation period (84 h), the keratinase production was enhanced from 41.62 U/mL to 401.67 ± 9.23 U/mL (9.65 fold increase) that corresponds to a feather degradation of 32.67 ± 1.36% was achieved. With regard to the cost effectiveness of application studies, the crude enzyme extracted from the optimized medium was tested for its potential dehairing, destaining and metal recovery properties. Complete dehairing was achieved within 48 h of treatment with crude enzyme without any visible damage to the collagen layer of goat skin. In destaining studies, combination of crude enzyme and detergent solution [1 mL detergent solution (5 mg/mL) and 1 mL crude enzyme] was found to be most effective in removing blood stains from cotton cloth. Silver recovery from used X-ray films was achieved within 6 min of treatment with crude enzyme maintained at 40 °C.

Evaluation of tea (Camellia sinensis L.) phytochemicals as multi-disease modulators, a multidimensional in silico strategy with the combinations of network pharmacology, pharmacophore analysis, statistics and molecular docking.

Tea (Camellia sinensis L.) is considered as to be one of the most consumed beverages globally and a reservoir of phytochemicals with immense health benefits. Despite numerous advantages, tea compounds lack a robust multi-disease target study. In this work, we presented a unique in silico approach consisting of molecular docking, multivariate statistics, pharmacophore analysis, and network pharmacology approaches. Eight tea phytochemicals were identified through literature mining, namely gallic acid, catechin, epigallocatechin gallate, epicatechin, epicatechin gallate (ECG), quercetin, kaempferol, and ellagic acid, based on their richness in tea leaves. Further, exploration of databases revealed 30 target proteins related to the pharmacological properties of tea compounds and multiple associated diseases. Molecular docking experiment with eight tea compounds and all 30 proteins revealed that except gallic acid all other seven phytochemicals had potential inhibitory activities against these targets. The docking experiment was validated by comparing the binding affinities (Kcal mol-1) of the compounds with known drug molecules for the respective proteins. Further, with the aid of the application of statistical tools (principal component analysis and clustering), we identified two major clusters of phytochemicals based on their chemical properties and docking scores (Kcal mol-1). Pharmacophore analysis of these clusters revealed the functional descriptors of phytochemicals, related to the ligand-protein docking interactions. Tripartite network was constructed based on the docking scores, and it consisted of seven tea phytochemicals (gallic acid was excluded) targeting five proteins and ten associated diseases. Epicatechin gallate (ECG)-hepatocyte growth factor receptor (PDB id 1FYR) complex was found to be highest in docking performance (10 kcal mol-1). Finally, molecular dynamic simulation showed that ECG-1FYR could make a stable complex in the near-native physiological condition.

Sesquiterpenoid-rich Java Ginger rhizome extract prompts autophagic cell death in cervical cancer cell SiHa mainly by modulating cellular redox homeostasis.

Java Ginger or Curcuma zanthorrhiza Roxb. has long gained focus among tribal people of Java, for its medicinal properties mainly against gynaecological challenges. The present study aims to identify the most potent phytocompound present in the extract and determine primary mode of action accountable for cytotoxic activity of Curcuma zanthorrhiza rhizome extract against HPV16-positive SiHa cervical cancer cells. The phytochemically-rich extract of rhizome (CZM) was capable to inhibit proliferation of target cells in a dose-dependent manner with an IC50 of 150 µg/ml. Dysregulation of intercellular antioxidant defence system resulted to surges in ROS and RNS level, increased calcium concentration and compromised mitochondrial membrane potential. Nucleus got affected, cell cycle dynamics got impaired while clonogenicity and migration ability diminished. Expression of viral oncogenes E7 and E6 decreased significantly. Accumulation of toxic cell metabolite and decrease in level of essential ones continued. Finally, alteration in PI3K/AKT/mTOR signalling route was followed by onset of autophagic cell death concomitant with the upregulated expression of Beclin1, Atg5-12 and LC3II. Curcumin and a novel crystal as well as few phyto-fractions were isolated by column chromatography. Of these, curcumin was found to be most potent in inducing cytotoxicity in SiHa while two other fractions also showed significant activity. Thus, CZM acted against SiHa cells by inducing autophagy that commences in compliance to the changes in PI3K/AKT/mTOR pathway mainly in response to oxidative stress. To the best of our knowledge this is the first report of Curcuma zanthorrhiza Roxb. inducing autophagy. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03415-9.

An in-silico pharmacophore-based molecular docking study to evaluate the inhibitory potentials of novel fungal triterpenoid Astrakurkurone analogues against a hypothetical mutated main protease of SARS-CoV-2 virus.

BACKGROUND: The main protease is an important structural protein of SARS-CoV-2, essential for its survivability inside a human host. Considering current vaccines' limitations and the absence of approved therapeutic targets, Mpro may be regarded as the potential candidate drug target. Novel fungal phytocompound Astrakurkurone may be studied as the potential Mpro inhibitor, considering its medicinal properties reported elsewhere. METHODS: In silico molecular docking was performed with Astrakurkurone and its twenty pharmacophore-based analogues against the native Mpro protein. A hypothetical Mpro was also constructed with seven mutations and targeted by Astrakurkurone and its analogues. Furthermore, multiple parameters such as statistical analysis (Principal Component Analysis), pharmacophore alignment, and drug likeness evaluation were performed to understand the mechanism of protein-ligand molecular interaction. Finally, molecular dynamic simulation was done for the top-ranking ligands to validate the result. RESULT: We identified twenty Astrakurkurone analogues through pharmacophore screening methodology. Among these twenty compounds, two analogues namely, ZINC89341287 and ZINC12128321 showed the highest inhibitory potentials against native and our hypothetical mutant Mpro, respectively (-7.7 and -7.3 kcal mol-1) when compared with the control drug Telaprevir (-5.9 and -6.0 kcal mol-1). Finally, we observed that functional groups of ligands namely two aromatic and one acceptor groups were responsible for the residual interaction with the target proteins. The molecular dynamic simulation further revealed that these compounds could make a stable complex with their respective protein targets in the near-native physiological condition. CONCLUSION: To conclude, Astrakurkurone analogues ZINC89341287 and ZINC12128321 can be potential therapeutic agents against the highly infectious SARS-CoV-2 virus.

In Silico Analysis of the Apoptotic and HPV Inhibitory Roles of Some Selected Phytochemicals Detected from the Rhizomes of Greater Cardamom.

Occurrence of cervical cancer, caused due to persistent human papilloma virus (HPV) infection, is common in women of developing countries. As the conventional treatments are expensive and associated with severe side effects, there is a need to find safer alternatives, which is affordable and less toxic to the healthy human cells. Present study aimed to evaluate the anti-HPV and apoptotic potential of four compounds from the greater cardamom (Amomum subulatum Roxb. var. Golsey), namely rhein, phytosphingosine, n-hexadecenoic acid and coronarin E. Their anti-HPV and apoptotic potential were studied against viral E6, E7 and few anti-apoptotic proteins of host cell (BCL2, XIAP, LIVIN) by in silico docking technique. Phytochemicals from the plant extract were analysed and identified by LC/MS and GC/MS. Involvement of the target proteins in various biological pathways was determined through KEGG. Structural optimization of the three-dimensional structures of the ligands (four phytochemicals and control drug) was done by Avogadro1.1. Receptor protein models were built using ProMod3 and other advanced tools. Pharmacophore modelling of the selected phytochemicals was performed in ZINCPharmer. Swiss ADME studies were undertaken to determine drug likeness. The ligands and proteins were digitally docked in DockThor docking program. Protein flexibility-molecular dynamic simulation helped to study protein-ligand stability in real time. Finally, the correlation of evaluated molecules was studied by the use of principal component analysis (PCA) based on the docking scores. All the ligands were found to possess apoptotic and anti-cancer activities and did not violate Lipinsky criteria. n-Hexadecanoic acid and its analogues showed maximum efficacy against the target proteins. All the protein-ligand interactions were found to be stable. The uncommon phytochemicals identified from rhizomes of greater cardamom have anti-cancer, apoptotic and HPV inhibitory potentials as analysed by docking and other in silico studies, which can be utilized in drug development after proper experimental validation.

Curcumin inhibits spike protein of new SARS-CoV-2 variant of concern (VOC) Omicron, an in silico study.

BACKGROUND: Omicron (B.1.1.529), a variant of SARS-CoV-2 is currently spreading globally as a dominant strain. Due to multiple mutations at its Spike protein, including 15 amino acid substitutions at the receptor binding domain (RBD), Omicron is a variant of concern (VOC) and capable of escaping vaccine generated immunity. So far, no specific treatment regime is suggested for this VOC. METHODS: The three-dimensional structure of the Spike RBD domain of Omicron variant was constructed by incorporating 15 amino acid substitutions to the Native Spike (S) structure and structural changes were compared that of the Native S. Seven phytochemicals namely Allicin, Capsaicin, Cinnamaldehyde, Curcumin, Gingerol, Piperine, and Zingeberene were docked with Omicron S protein and Omicron S-hACE2 complex. Further, molecular dynamic simulation was performed between Crcumin and Omicron S protein to evaluate the structural stability of the complex in the physiological environment and compared with that of the control drug Chloroquine. RESULTS: Curcumin, among seven phytochemicals, was found to have the most substantial inhibitory potential with Omicron S protein. Further, it was found that curcumin could disrupt the Omicron S-hACE2 complex. The molecular dynamic simulation demonstrated that Curcumin could form a stable structure with Omicron S in the physiological environment. CONCLUSION: To conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.

PA1 cells containing a truncated DNA polymerase ß protein are more sensitive to gamma radiation.

PURPOSE: DNA polymerase ß (Polß) acts in the base excision repair (BER) pathway. Mutations in DNA polymerase ß (Polß) are associated with different cancers. A variant of Polß with a 97 amino acid deletion (PolßΔ), in heterozygous conditions with wild-type Polß, was identified in sporadic ovarian tumor samples. This study aims to evaluate the gamma radiation sensitivity of PolßΔ for possible target therapy in ovarian cancer treatment. MATERIALS AND METHODS: PolßΔ cDNA was cloned in a GFP vector and transfected in PA1 cells. Stable cells (PA1PolßΔ) were treated with 60Co sourced gamma-ray (0-15 Gy) to investigate their radiation sensitivity. The affinity of PolßΔ with DNA evaluated by DNA protein in silico docking experiments. RESULTS: The result showed a statistically significant (p < 0.05) higher sensitivity towards radiation at different doses (0-15 Gy) and time-point (48-72 hours) for PA1PolßΔ cells in comparison with normal PA1 cells. Ten Gy of gamma radiation was found to be the optimal dose. Significantly more PA1PolßΔ cells were killed at this dose than PA1 cells after 48 hours of treatment via an apoptotic pathway. The in silico docking experiments revealed that PolßΔ has more substantial binding potential towards the dsDNA than wild-type Polß, suggesting a possible failure of BER pathway that results in cell death. CONCLUSION: Our study showed that the PA1PolßΔ cells were more susceptible than PA1 cells to gamma radiation. In the future, the potentiality of ionizing radiation to treat this type of cancer will be checked in animal models.

In silico study of some selective phytochemicals against a hypothetical SARS-CoV-2 spike RBD using molecular docking tools.

BACKGROUND: This world is currently witnessing a pandemic outbreak of 'COVID-19' caused by a positive-strand RNA virus 'SARS-CoV-2'. Millions have succumbed globally to the disease, and the numbers are increasing day by day. The viral genome enters into the human host through interaction between the spike protein (S) and host angiotensin-converting enzyme-2 (ACE2) proteins. S is the common target for most recently rolled-out vaccines across regions. A recent surge in single/multiple mutations in S region is of great concern as it may escape vaccine induced immunity. So far, the treatment regime with repurposed drugs has not been too successful. HYPOTHESIS: Natural compounds are capable of targeting mutated spike protein by binding to its active site and destabilizing the spike-host ACE2 interaction. MATERIALS AND METHODS: A hypothetical mutated spike protein was constructed by incorporating twelve different mutations from twelve geographical locations simultaneously into the receptor-binding domain (RBD) and docked with ACE2 and seven phytochemicals namely allicin, capsaicin, cinnamaldehyde, curcumin, gingerol, piperine and zingeberene. Molecular Dynamic (MD) simulation and Principal Component Analysis (PCA) were finally used for validation of the docking results. RESULT: The docking results showed that curcumin and piperine were most potent to bind ACE2, mutated spike, and mutated spike-ACE2 complex, thereby restricting viral entry. ADME analysis also proved their drug candidature. The docking complexes were found to be stable by MD simulation. CONCLUSION: This result provides a significant insight about the phytochemicals' role, namely curcumin and piperine, as the potential therapeutic entities against mutated spike protein of SARS-CoV-2.

Phytochemicals as potential drug candidates for targeting SARS CoV 2 proteins, an in silico study.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a member of the family Coronaviridae, and the world is currently witnessing a global pandemic outbreak of this viral disease called COVID-19. With no specific treatment regime, this disease is now a serious threat to humanity and claiming several lives daily. In this work, we selected 24 phytochemicals for an in silico docking study as candidate drugs, targeting four essential proteins of SARS-CoV-2 namely Spike glycoprotein (PDB id 5WRG), Nsp9 RNA binding protein (PDB id 6W4B), Main Protease (PDB id 6Y84), and RNA dependent RNA Polymerase (PDB id 6M71). After statistical validation, the results indicated that a total of 11 phytochemicals divided into two clusters might be used as potential drug candidates against SARS-CoV-2. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-021-00654-x.