Synthesis, molecular docking and ADMET prediction of novel swertiamarin analogues for the restoration of type-2 diabetes: an enzyme inhibition assay.

Swertiamarin is a lead, biologically active compound obtained from Enicostemma littorale Blume and known to be identified for the anti-diabetic activity. Present work comprises the synthesis and structural optimization of seven novel swertiamarin analogues and those were not being reported elsewhere till date. Swertiamarin was isolated, followed by modifications that have been accomplished amidst fluorinating, acetylating and oxidizing agents and also performed chromatographic purity and characterization of analogues. Furthermore, the swertiamarin analogues were screened for dipeptidyl peptidase IV (DPP-IV) enzyme inhibition with in silico studies. Besides, the pharmacokinetics and toxicity of analogues were predicted using ADMET software. In a nutshell, the compounds such as SNIPERSV-4 and SNIPERSV-7 have to pose good initial activity (∼48%) in comparison to standard DPP-IV inhibitor (Sitagliptin). The identified analogues were active against DPP-IV enzyme in preliminary screenings, and these findings would be beneficial for the new age researchers also for the therapy of diabetes.

Exploring AyuGenomics approach for understanding COVID-19 predisposition and progression.

Recent reports on COVID-19 suggest that, the susceptibility to COVID-19 infection and its progression have a genetic predisposition. Majorly associated genetic variants are found in human leukocyte antigen (HLA), angiotensin convertase enzyme (ACE; rs1799752: ACE2; rs73635825), and transmembrane protease serine 2 (TMPRSS-2; rs12329760) genes. Identifying highly prone population having these variants is imperative for determining COVID-19 therapeutic strategies. Ayurveda (Indian traditional system of medicine) concept of Prakriti holds potential to predict genomic and phenotypic variations. Reported work on Prakriti correlates HLA-DR alleles with three broad phenotypes (Tridosha) described in Ayurveda (AyuGenomics). This is suggestive of differences in immune responses in individuals with specific constitutions. Therefore, the reported studies provide clues for clinically relevant hypotheses to be tested in systematic studies. The proposed approach of Ayurveda-based phenotype screening may offer a way ahead to design customized strategies for management of COVID-19 based on differences in Prakriti, immune response, and drug response. However, this needs clinical evaluation of the relation between Prakriti and genetic or phenotypic variants in COVID-19 prone and resistant populations.

Ayurveda botanicals in COVID-19 management: An in silico multi-target approach.

The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. Ayurvedic Rasayana therapy has been traditionally used in India for its immunomodulatory and adaptogenic effects, and more recently has been included as therapeutic adjuvant for several maladies. Amongst several others, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) play an important role in Rasayana therapy. The objective of this study was to explore the immunomodulatory and anti SARS-CoV2 potential of phytoconstituents from Ashwagandha, Guduchi and Shatavari using network pharmacology and docking. The plant extracts were prepared as per ayurvedic procedures and a total of 31 phytoconstituents were identified using UHPLC-PDA and mass spectrometry studies. To assess the immunomodulatory potential of these phytoconstituents an in-silico network pharmacology model was constructed. The model predicts that the phytoconstituents possess the potential to modulate several targets in immune pathways potentially providing a protective role. To explore if these phytoconstituents also possess antiviral activity, docking was performed with the Spike protein, Main Protease and RNA dependent RNA polymerase of the virus. Interestingly, several phytoconstituents are predicted to possess good affinity for the three targets, suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would not be adverse herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals as therapeutic adjuvants in the management of COVID-19 following rigorous experimental validation.

Advancements in Cancer Stem Cell Isolation and Characterization.

Occurrence of stem cells (CSCs) in cancer is well established in last two decades. These rare cells share several properties including presence of common surface markers, stem cell markers, chemo- and radio- resistance and are highly metastatic in nature; thus, considered as valuable prognostic and therapeutic targets in cancer. However, the studies related to CSCs pave number of issues due to rare cell population and difficulties in their isolation ascribed to common stem cell marker. Various techniques including flow cytometry, laser micro-dissection, fluorescent nanodiamonds and microfluidics are used for the isolation of these rare cells. In this review, we have included the advance strategies adopted for the isolation of CSCs using above mentioned techniques. Furthermore, CSCs are primarily found in the core of the solid tumors and their microenvironment plays an important role in maintenance, self-renewal, division and tumor development. Therefore, in vivo tracking and model development become obligatory for functional studies of CSCs. Fluorescence and bioluminescence tagging has been widely used for transplantation assay and lineage tracking experiments to improve our understanding towards CSCs behaviour in their niche. Techniques such as Magnetic resonance imaging (MRI) and Positron emission tomography (PET) have proved useful for tracking of endogenous CSCs which could be helpful in their identification in clinical settings.