Previous studies suggest that berberine, an isoquinoline alkaloid, has antiviral potential and is a possible therapeutic candidate against SARS-CoV-2. The molecular underpinnings of its action are still unknown. Potential targets include quadruplexes (G4Q) in the viral genome as they play a key role in modulating the biological activity of viruses. While several DNA-G4Q structures and their binding properties have been elucidated, RNA-G4Qs such as RG-1 of the N-gene of SARS-CoV-2 are less explored. Using biophysical techniques, the berberine binding thermodynamics and the associated conformational and hydration changes of RG-1 could be characterized and compared with human telomeric DNA-G4Q 22AG. Berberine can interact with both quadruplexes. Substantial changes were observed in the interaction of berberine with 22AG and RG-1, which adopt different topologies that can also change upon ligand binding. The strength of interaction and the thermodynamic signatures were found to dependent not only on the initial conformation of the quadruplex, but also on the type of salt present in solution. Since berberine has shown promise as a G-quadruplex stabilizer that can modulate viral gene expression, this study may also contribute to the development of optimized ligands that can discriminate between binding to DNA and RNA G-quadruplexes. 相似文献
RNA is a unique biomolecule that is involved in a variety of fundamental biological functions, all of which depend solely on its structure and dynamics. Since the experimental determination of crystal RNA structures is laborious, computational 3D structure prediction methods are experiencing an ongoing and thriving development. Such methods can lead to many models; thus, it is necessary to build comparisons and extract common structural motifs for further medical or biological studies. Here, we introduce a computational pipeline dedicated to reference-free high-throughput comparative analysis of 3D RNA structures. We show its application in the RNA-Puzzles challenge, in which five participating groups attempted to predict the three-dimensional structures of 5- and 3-untranslated regions (UTRs) of the SARS-CoV-2 genome. We report the results of this puzzle and discuss the structural motifs obtained from the analysis. All simulated models and tools incorporated into the pipeline are open to scientific and academic use. 相似文献
Background: Breast cancer is the most common cancer in women globally, and diagnosing it early and finding potential drug candidates against multi-drug resistant metastatic breast cancers provide the possibilities of better treatment and extending life. Methods: The current study aimed to evaluate the synergistic anti-metastatic activity of Curcumin (Cur) and Paclitaxel (Pacli) individually, the combination of Curcumin–Paclitaxel (CP), and also in conjugation with gold nanoparticles (AuNP–Curcumin (Au-C), AuNP–Paclitaxel (Au-P), and AuNP–Curcumin–Paclitaxel (Au-CP)) in various in vitro and in vivo models. Results: The results from combination treatments of CP and Au-CP demonstrated excellent synergistic cytotoxic effects in triple-negative breast cancer cell lines (MDA MB 231 and 4T1) in in vitro and in vivo mouse models. Detailed mechanistic studies were performed that reveal that the anti-cancer effects were associated with the downregulation of the expression of VEGF, CYCLIN-D1, and STAT-3 genes and upregulation of the apoptotic Caspase-9 gene. The group of mice that received CP combination therapy (with and without gold nanoparticles) showed a significant reduction in the size of tumor when compared to the Pacli alone treatment and control groups. Conclusions: Together, the results suggest that the delivery of gold conjugated Au-CP formulations may help in modulating the outcomes of chemotherapy. The present study is well supported with observations from cell-based assays, molecular and histopathological analyses. 相似文献
Drug delivery to a target without adverse effects is one of the major criteria for clinical use. Herein, we have made an attempt to explore the delivery efficacy of SDS surfactant in a monomer and micellar stage during the delivery of the model drug, Toluidine Blue (TB) from the micellar cavity to DNA. Molecular recognition of pre-micellar SDS encapsulated TB with DNA occurs at a rate constant of k1 ∼652 s−1. However, no significant release of encapsulated TB at micellar concentration was observed within the experimental time frame. This originated from the higher binding affinity of TB towards the nano-cavity of SDS at micellar concentration which does not allow the delivery of TB from the nano-cavity of SDS micelles to DNA. Thus, molecular recognition controls the extent of DNA recognition by TB which in turn modulates the rate of delivery of TB from SDS in a concentration-dependent manner. 相似文献
In this paper, we present an algo-rithm for capacity optimization in intelligent reflecting surface (IRS)-based multiple-input multiple-output (MIMO) communicat... 相似文献
The effects of different parameters such as time, concentration, pH and temperature, on metal ion retention properties of the polymer have been investigated. Metal ion adsorption kinetics, isotherms and thermodynamics have been studied. A plausible mechanism for mercury ion retention has been suggested. Mercuric ion has been isolated quantitatively from various synthetic mixture containing metal ions (Ni2+, Cd2+, Pb2+ and Zn2+). 相似文献
The quantum-dot cellular automata (QCA) is considered to be one of the ground-breaking nanotechnologies developed over the last two decades. A layered T (LT) logic cell library is constructed herein, and the methodology is extended to generic adder and subtractor module designs. The two proposed algorithms lead to more efficient QCA layout designs for an n-bit ripple carry adder (RCA) and subtractor based on an effective clock zone assignment approach. The suggested one-, four-, and eight-bit RCAs and subtractors surpass most of their existing counterparts by offering lower effective area and cell complexity. A comparative analysis is presented regarding the complexity, irreversible power dissipation, and Costα of the proposed n-bit layouts from a cost estimation purview.
Reactivity of different medium-chain substrates, i.e., n-octanol, caprylic acid, and its alkyl (methyl, ethyl, n-propyl, and n-butyl) esters, was assessed in the interesterification of tripalmitin catalyzed by papaya (Carica papaya) lipase. Alcoholysis with n-octanol was the fastest reaction leading to the highest conversion of tripalmitin to n-octyl palmitate and concomitant formation of di- as well as monopalmitoylglycerols. This was followed by transesterification
of tripalmitin with n-butyl and n-propyl caprylates, which in turn were faster than transesterification with ethyl and methyl caprylates, yielding in each
case the corresponding alkyl palmitates and triacylglycerols containing palmitoyl and capryloyl moieties as the major reaction
products. Acidolysis of tripalmitin with caprylic acid yielded palmitic acid and triacylglycerols containing palmitoyl and
capryloyl moieties as the major reaction products, however, with the lowest conversion among the three interesterification
reactions studied. In each case, interesterification was accompanied by some hydrolysis of tripalmitin. 相似文献