Is Daclatasvir a suitable substitute for Amphotericin B in the treatment of Mucormycosis when Amphotericin B is scarce?

BACKGROUND: Mucormycosis has been infesting the universe for a while back, often with no prompt treatments. The disease devastation is spreading at an alarming rate. Many researchers are still hoping for a good potential drug that could help the healthcare system in this tussle. Molecular docking is an in silico tool that has gained popularity over the last few decades. Knowing the mechanism of enzymatic action is aided by imitating membrane protein actions in binding ligands. AIM: The aim of this perspective is to determine whether an existing drug, daclatasvir, has antifungal activity. OBJECTIVE: The primary objective of this in silico study was to investigate the potential effects of the binding affinity of daclatasvir with the crucial protein (1XFF) of mucormycosis, as well as the binding pattern of the active site amino acids with the drug molecule. MATERIALS AND METHODS: To calculate the binding affinity of daclatasvir to the fungal protein 1XFF, Auto Dock Vina was used for molecular docking studies. The CDOCKER protocol was used to determine the receptor-ligand interaction by configuring various parameters. RESULTS: The docking energy of the ligand (daclatasvir) on the protein (1XFF) was found to be -16.7216 kcal/mol, while the interaction energy was found to be - 42.1314 kcal/mol. CONCLUSION: The binding pattern completely alters the dynamics of the protein, resulting in the breakdown of the fungal wall. The vital protein (1XFF) of Rhizopus oryzae is proposed as a possible protein target for the non-structural protein 5A inhibitor/antiviral drug daclatasvir in this study.

Anxiolytic effects of silibinin and naringenin on zebrafish model: A preclinical study.

OBJECTIVE: Stress exacerbates the pathophysiology of major neurodegenerative disorders. In this study, the zebrafish (Danio rerio), the frequently used model for experimental studies of stress and other central nervous system disorders, was used to evaluate the anxiolytic potential of flavonoids, namely silibinin and naringenin on alleviating acute stress-induced anxiety. MATERIALS AND METHODS: A molecular docking study with Molegro Virtual Docker software was done to assess the binding potential of flavonoids on serotonin and dopamine receptors. To determine the bioactivity and investigate the toxicity of the flavonoids, silibinin, and naringenin, brine shrimp lethality assay, and an acute toxicity study was conducted according to Organization for Economic Co-operation and Development (OECD) Test Guideline 203. The effect of silibinin and naringenin was assessed using behavioral tasks such as the novel tank assay and the light-dark test on the zebrafish model of acute stress. RESULTS: Molecular docking studies showed a higher affinity of silibinin and naringenin for the serotonin and dopamine receptors. In comparison to the LC50 value, 13.15 µg/ml of the reference standard potassium dichromate, silibinin, and naringenin yielded higher LC50 values, 34.10 µg/ml and 91.33 µg/ml, respectively. The LC50 value of silibinin and naringenin was observed to be >100 mg/l from the acute toxicity study on adult zebrafish. After transferring to a novel tank, silibinin and naringenin-treated zebrafish groups were found to explore the upper level of the tank, similar to standard drugs, and spent a long time in the upper level of the tank compared to the control group (p < 0.01). Both silibinin and naringenin treatment group spent increased amounts of time in the tank's illuminated part in contrast to that of the dark side as evidenced by the number of zebrafish entering or remaining in the illuminated part of the tank through the light-dark test. Silibinin and naringenin treated groups were found to spend increased time in the light side significantly on the day 15th of evaluation as compared to the control group (p < 0.05 and p < 0.001, respectively). CONCLUSION: The flavonoids, silibinin, and naringenin were found to mitigate acute stress-induced anxiety, owing to their anxiolytic properties in the zebrafish model and may be explored as the potential therapeutic agents for treating anxiety.

Colorimetric sensors for rapid detection of various analytes.

Sensor technology for the rapid detection of the analytes with high sensitivity and selectivity has several challenges. Despite the challenges, colorimetric sensors have been widely accepted for its high sensitive and selective response towards various analytes. In this review, colorimetric sensors for the detection of biomolecules like protein, DNA, pathogen and chemical compounds like heavy metal ions, toxic gases and organic compounds have been elaborately discussed. The visible sensing mechanism based on Surface Plasmon Resonance (SPR) using metal nanoparticles like Au, Ag, thin film interference using SiO2 and colorimetric array-based technique have been highlighted. The optical property of metal nanoparticles enables a visual color change during its interaction with the analytes owing to the dispersion and aggregation of nanoparticles. Recently, colorimetric changes using silica substrate for detection of protein and small molecules by thin film interference as a visible sensing mechanism has been developed without the usage of fluorescent or radioisotopes labels. Multilayer of biomaterials were used as a platform where reflection and interference of scattering light occur due to which color change happens leading to rapid sensing. Colorimetric array-based technique for the detection of organic compounds using chemoresponsive dyes has also been focused wherein the interaction of the analytes with the substrate coated with chemoresponsive dyes gives colorimetric change.

Co-encapsulated resveratrol and quercetin in chitosan and peg modified chitosan nanoparticles: For efficient intra ocular pressure reduction.

Natural anti-oxidants resveratrol (RES) and quercetin (QUR) posses the ability to reduce intra ocular pressure efficiently. Concurrent administration of RES and QUR was able to enhance the bioavailability of RES. Present research work describes upsurge of QUR in RES loaded chitosan (CS) nanoparticles (NPs) and polyethylene glycol (PEG) modified CS NPs for improved delivery and synergic effects on reducing intra ocular pressure for the treatment of glaucoma. CS NPs and PEG modified CS NPs were prepared by ionic gelation of tripolyphosphate and CS. The synthesised NPs were spherical in shape and RES entrapment and loading efficiency in the formulation decreased with increasing PEG concentration. Particle size of the formulation increased while incorporating PEG and drugs. The crystalline nature of RES and QUR changed in the NPs and that was confirmed by XRD study. Free radical neutralising efficiency improved while incorporating QUR in the formulation. Ex-vivo corneal permeation of RES was higher from RES and QUR loaded formulation than RES alone containing NPs and free RES dispersion. RES and QUR loaded PEG modified CS NPs showed sustained and enhanced reduction of intra ocular pressure (5.5±0.5mmHg) in normotensive rabbits.

Colloidal synthesis and electrical behaviour of n-ZnGdO/p-Si heterojunction diodes.

Studies on manoeuvring the optoelectronic characteristics of a semiconducting nanostructure are of recent specific interest for a wide range of photonic applications. In this regard, the optical and electrical characteristics of ZnO nanostructures have been tuned and studied systematically using Gd ions. The structural and morphological characteristics of the solution processed ZnGdO nanostructures were studied in detail using the results of X-ray diffraction and microscopic measurements. The absorption band edge in ZnO was noted to shift towards the lower wavelength values on Gd substitution, suggesting an increase in its energy band gap. The blue emissivity from ZnO complexes was also noted to improve as a function of Gd composition in ZnO. The potential of ZnGdO nanostructures for optoelectronic functions was evaluated by fabricating heterojunction diodes based on n-ZnGdO/p-Si. The diode characteristics revealed an improved electrical conductivity and rectifying behaviour from the fabricated architectures upon Gd substitution and photon illumination. The findings are correlated with the increased charge carrier concentration and defect states existing within ZnGdO species, through appropriate mechanisms.