Therapeutic role of mTOR inhibitors in control of SARS-CoV-2 viral replication.

By the end of 2019, COVID-19 was reported in Wuhan city of China, and through human-human transmission, this virus spread worldwide and became a pandemic. Initial symptoms of the disease include fever, cough, loss of smell, taste, and shortness of breath, but a decrease in the oxygen levels in the body leads, and pneumonia may ultimately lead to the patient's death. However, the symptoms vary from patient to patient. To understand COVID-19 disease pathogenesis, researchers have tried to understand the cellular pathways that could be targeted to suppress viral replication. Thus, this article reviews the markers that could be targeted to inhibit viral replication by inhibiting the translational initiation complex/regulatory kinases and upregulating host autophagic flux that may lead to a reduction in the viral load. The article also highlights that mTOR inhibitors may act as potential inhibitors of viral replication. mTOR inhibitors such as metformin may inhibit the interaction of SARS-CoV-2 Nsp's and ORFs with mTORC1, LARP1, and 4E-BP. They may also increase autophagic flux by decreasing protein degradation via inhibition of Skp2, further promoting viral cell death. These events result in cell cycle arrest at G1 by p27, ultimately causing cell death.

Ethanolic Extract of Artemisia vulgaris Leaf Promotes Apoptotic Cell Death in Non-Small-Cell Lung Carcinoma A549 Cells through Inhibition of the Wnt Signaling Pathway.

The Wnt signaling pathway is reported to be associated with lung cancer progression, metastasis and drug resistance, and thus it is an important therapeutic target for lung cancer. Plants have been shown as reservoirs of multiple potential anticancer agents. In the present investigation, the ethanolic leaf extract of Artemisia vulgaris (AvL-EtOH) was initially analyzed by means of gas chromatography-mass spectrometry (GC-MS) to identify the important phytochemical constituents. The GC-MS analysis of AvL-EtOH exhibited 48 peaks of various secondary metabolites such as terpenoids, flavonoids, carbohydrates, coumarins, amino acids, steroids, proteins, phytosterols, and diterpenes. It was found that the treatment with increasing doses of AvL-EtOH suppressed the proliferation and migration of lung cancer cells. Furthermore, AvL-EtOH induced prominent nuclear alteration along with a reduction in mitochondrial membrane potential and increased ROS (reactive oxygen species) generation in lung cancer cells. Moreover, AvL-EtOH-treated cells exhibited increased apoptosis, demonstrated by the activation of caspase cascade. AvL-EtOH also induced downregulation of Wnt3 and ß-catenin expression along with cell cycle protein cyclin D1. Thus, the results of our study elucidated the potential of bioactive components of Artemisia vulgaris in the therapeutic management of lung cancer cells.

Microbial Beta Glucosidase Enzymes: Recent Advances in Biomass Conversation for Biofuels Application.

The biomass to biofuels production process is green, sustainable, and an advanced technique to resolve the current environmental issues generated from fossil fuels. The production of biofuels from biomass is an enzyme mediated process, wherein ß-glucosidase (BGL) enzymes play a key role in biomass hydrolysis by producing monomeric sugars from cellulose-based oligosaccharides. However, the production and availability of these enzymes realize their major role to increase the overall production cost of biomass to biofuels production technology. Therefore, the present review is focused on evaluating the production and efficiency of ß-glucosidase enzymes in the bioconversion of cellulosic biomass for biofuel production at an industrial scale, providing its mechanism and classification. The application of BGL enzymes in the biomass conversion process has been discussed along with the recent developments and existing issues. Moreover, the production and development of microbial BGL enzymes have been explained in detail, along with the recent advancements made in the field. Finally, current hurdles and future suggestions have been provided for the future developments. This review is likely to set a benchmark in the area of cost effective BGL enzyme production, specifically in the biorefinery area.

Phytochemical Study of Aegle marmelos: Chromatographic Elucidation of Polyphenolics and Assessment of Antioxidant and Cytotoxic Potential.

BACKGROUND: The antioxidant potential of medicinal plants has been illustrated through many reports clearly depicting that plants are a rich source of antioxidants, making them a great resource of novel drugs and health-care products. OBJECTIVES: The current study is, therefore, focused toward the assessment of antioxidant properties along with the presence of phytochemicals in leaves of 18 varieties/accessions of Aegle marmelos. MATERIALS AND METHODS: The antioxidant activities were initially measured using superoxide radical scavenging method, 2, 2-diphenyl-1-picrylhydrazyl (DPPH), and ferric-reducing ability of plasma assays. Further, thin-layer chromatography (TLC), high-performance TLC, and column chromatography were performed to isolate the potentially active fraction and anti-inflammatory activity of crude, and the isolated fraction was tested on J774 macrophage cell line. RESULTS: The maximum inhibition of superoxide anions was shown by Pant Aparna. Additionally, Pant Aparna extract was most efficient, exhibiting 92.0% inhibition in scavenging the DPPH radicals. The content of total carotenoids was found to be higher in Pant Aparna among all the varieties/accessions. Furthermore, the crude extract and the fraction A. marmelos methanolic fraction 21 (AMMF21) were found to be nontoxic and significant reactive oxygen species, and NO inhibition was observed in a concentration-dependent manner. Moreover, the methanolic extract of variety Pant Aparna showed promising in vitro antioxidant activity, indicating its potency for therapeutic applications. CONCLUSION: In brief, this is the first ever report on Pant Aparna as the best variety in terms of phytocompounds and identification of potential antioxidant activity. In addition, the AMMF21 fraction of methanolic extract possessing best antioxidant activity on macrophage cells indicates its use as a novel phytotherapeutic agent. SUMMARY: Our study identifies the best variety/accession of Aegle marmelos possessing the potential antioxidant and reactive oxygen species scavenging activity possessed by the methanolic crude extract of variety Pant Aparna along with the fraction A. marmelos methanolic fraction 21 isolated through column chromatography on J774 murine macrophage cell lineThe high-performance thin-layer chromatography fingerprinting profile obtained acts as a diagnostic tool to identify and determine the quality and purity of this extract and fraction in future studiesOn the basis of the results obtained, the above variety should be taken further to exploit its immense potential for other biological activities of medicinal importancePant Aparna is an outstanding variety of A. marmelos and should be extensively studied for isolation of a novel and potential therapeutic agent. Abbreviations used: AMMF21: Aegle marmelos methanolic fraction 21, DPPH: (2, 2-diphenyl-1-picrylhydrazyl), FRAP: Ferric-reducing ability of plasma, HP-TLC: High-performance-thin-layer chromatography, TLC: Thin-layer chromatography, TCA: Trichloroacetic acid, TPTZ: 2,4,6-Tripyridyl-s-triazine, DNPH: 2,4-dinitrophenyl hydrazine, NBT: Nitroblue tetrazolium, NADH: Nicotinamide adenine dinucleotide, PMS: Phenazine metho-sulfate, DMEM: Dulbecco's modified Eagle medium; MTT: (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide, DCFDA: 2',7'-dichlorofluorescein diacetate, LPS: Lipopolysaccharide, NED: N-(1-Naphthyl) ethylenediamine.