Small RNA sequencing and identification of Andrographis paniculata miRNAs with potential cross­kingdom human gene targets.

Cross-species post-transcriptional regulatory potential of plant derived small non-coding microRNAs (miRNAs) has been well documented by plenteous studies. MicroRNAs are transferred to host cells via oral ingestion wherein they play a decisive role in regulation of host genes; thus, miRNAs have evolved as the nascent bioactive molecules imparting pharmacological values to traditionally used medicinal plants. The present study aims to investigate small RNA profiling in order to uncover the potential regulatory role of miRNAs derived from Andrographis paniculata, one of the most widely used herb by tribal communities for liver disorders and document the pharmacological properties of A. paniculata miRNAs. In this study, high-throughput sequencing method was used to generate raw data, ~ 60 million sequences were generated from A. paniculata leaves. Using computational tools and bioinformatics approach, analyses of 3,480,097 clean reads resulted in identification of 3440 known and 51 putative novel miRNAs regulating 1365 and 192 human genes respectively. Remarkably, the identified plausible novel miRNAs apa-miR-5, apa-miR-1, apa-miR-26, and apa-miR-30 are projected to target significant host genes including CDK6, IKBKB, TRAF3, CHD4, MECP2, and ADIPOQ. Subsequent annotations revealed probable involvement of the target genes in various pathways for instance p38-MAPK, AKT, AMPK, NF-Kß, ERK, WNT signalling, MYD88 dependant cascade, and pathways in cancer. Various diseases such as human papilloma virus infection, Alzheimer's, Non-alcoholic Fatty Liver, Alcoholic liver diseases, HepatoCellular Carcinoma (HCC), and numerous other cancers were predominantly found to be linked with target genes. Our findings postulate novel interpretations regarding modulation of human transcripts by A. paniculata miRNAs and exhibit the regulation of human diseases by plant-derived miRNAs. Though our study elucidates miRNAs as novel therapeutic agents, however, experimental validations for assessment of therapeutic potential of these miRNAs are still warranted.

Phenocam observed flowering anomaly of Rhododendron arboreum Sm. in Himalaya: a climate change impact perspective.

Flowering exhibits a significant relationship with environmental stimuli and changes. Effect of photoperiodism and vernalization have been well studied in flowering phenology; however, the effect of soil temperature on flowering is less explored which is one of the major factors of vegetation growth in alpine ecosystem. This study thus focuses on the effects of soil and air temperature on flowering response of Rhododendron arboreum Sm., a Himalayan tree species, which is also an indicator of spring initiation in high altitude regions. To monitor the flowering pattern, we employed automated phenocam, which was set up at 3356 masl in Tungnath (Indian Alpine region of Uttarakhand) for time-lapse photography of timberline ecotone. Soil and air temperature were recorded continuously at the timberline ecotone. Three years (2017 to 2020) of datasets were used for the present study. The phenocam observations displayed an interesting event in the year 2019-2020 with complete absence of flowering in R. arboreum population at Tungnath timberline ecotone. From the soil temperature data, an increase in winter (Dec-Jan, during which floral buds form) soil temperature, by > 1 °C, and no accumulation of freezing degree-days were found for the year 2019-2020. Air temperature however did not display any relationship with the failure of flowering, ruling out aerial chilling or frost injury of floral buds. From the results, a possible relationship between soil temperature and flowering can be suggested pointing towards necessary root apex vernalization stimulus in shallow rooted Rhododendrons. However, the dependency of flowering in Rhododendrons on winter soil temperature further requires continuous monitoring and more observations to make concrete inferences.

Pinpointing the potential hits for hindering interaction of SARS-CoV-2 S-protein with ACE2 from the pool of antiviral phytochemicals utilizing molecular docking and molecular dynamics (MD) simulations.

SARS-CoV-2, the viral particle, is responsible for triggering the 2019 Coronavirus disease outbreak (COVID-19). To tackle this situation, a number of strategies are being devised to either create an antidote, a vaccine, or agents capable of preventing its infection. To enable research on these strategies, numerous target proteins are identified where Spike (S) protein is presumed to be of immense potential. S-protein interacts with human angiotensin-converting-enzyme-2 (ACE2) for cell entry. The key region of S-protein that interacts with ACE2 is a portion of it designated as a receptor-binding domain (RBD), following whereby the viral membrane fuses with the alveolar membrane to enter the human cell. The proposition is to recognize molecules from the bundle of phytochemicals of medicinal plants known to possess antiviral potentials as a lead that could interact and mask RBD, rendering them unavailable to form ACE2 interactions. Such a molecule is called the 'S-protein blocker'. A total of 110 phytochemicals from Withania somnifera, Asparagus racemosus, Zinziber officinalis, Allium sativum, Curcuma longa and Adhatoda vasica were used in the study, of which Racemoside A, Ashwagandhanolide, Withanoside VI, Withanoside IV and Racemoside C were identified as top five hits using molecular docking. Further, essential Pharmacophore features and their ADMET profiles of these compounds were studied following to which the best three hits were analyzed for their interaction with RBD using Molecular Dynamics (MD) simulation. Binding free energy calculations were performed using MM/GBSA, proving these phytochemicals can serve as S-protein blocker.

Monitoring bio-optical response of coastal waters surrounding the Indian subcontinent to atmospheric dust deposition using satellite data.

The paper investigates the impact of atmospheric dust deposition on ocean biological productivity in association with oceanic supply of nutrients over specific regions of the Arabian Sea (20°N, 69°E) and the Bay of Bengal (20°N, 87°E) during wintertime (November-March) from the year 2012 to 2017 using satellite-based observations. During winter, selected regions are characterized by higher Chlorophyll-a (Chl-a) and major oceanic vertical supply of nutrients. Moderate Resolution Imaging Spectroradiometer onboard Aqua space-platform is used to obtain Chl-a and aerosol optical depth (AOD) data. Blended Chl-a daily product from various satellite sensors is also used. There are a total of nine cases (seven cases of the Arabian Sea region and two cases of the Bay of Bengal region) where episodic Chl-a enhancements following high AOD values are observed. Chl-a maxima lag behind AOD maxima by 1 to 4 days. Modern-Era Retrospective analysis for Research and Applications (Version-2) is used for AOD and dust deposition flux estimation. Estimated dust deposition flux ranges between 0.44 and 27.68 mg m-2 day-1.

MDCKpred: a web-tool to calculate MDCK permeability coefficient of small molecule using membrane-interaction chemical features.

Structure-based models to understand the transport of small molecules through biological membrane can be developed by enumerating intermolecular interactions of the small molecule with a biological membrane, usually a dimyristoylphosphatidylcholine (DMPC) monolayer. This ADME (absorption, distribution, metabolism, and excretion) property based on Madin-Darby Canine Kidney (MDCK) cell line demonstrates intestinal drug absorption of small molecules and correlated to human intestinal absorption which acts as a determining factor to forecast small-molecule prioritization in drug-discovery projects. We present here the development of MDCKpred web-tool which calculates MDCK permeability coefficient of small molecule based on the regression model, developed using membrane-interaction chemical features. The web-tool allows users to calculate the MDCK permeability coefficient (nm/s) instantly by providing simple descriptor inputs. The chemical-interaction features are derived from different parts of the DMPC molecule viz. head, middle, and tail regions and accounts overall intermolecular contacts of the small molecule when passively diffused through the phospholipid-rich biological membrane. The MDCKpred model is both internally (R2 = .76; [Formula: see text]= .68; Rtrain = .87; Rtest = .69) and externally (Rext = .55) validated. Furthermore, we used natural molecules as application examples to demonstrate its utility in lead exploration and optimization projects. The MDCKpred web-tool can be accessed freely at http://www.mdckpred.in . This web-tool is designed to offer an intuitive way of prioritizing small molecules based on calculated MDCK permeabilities.

Receptor-Guided De Novo Design of Dengue Envelope Protein Inhibitors.

Inhibitor design associated with the dynamics of dengue envelope protein at pre-fusion stage is a prominent strategy to interfere fusion transition of dengue virus with the host cell membrane. Receptor-guided de novo inhibitors were designed based on the knowledge of co-crystallized detergent, ß-octyl glucoside. Pharmacophore features distribution showed the preference of aromatic groups with H bonding features connected to aliphatic bulky group as the skeleton for inhibitor design. Molecular dynamic simulations revealed (2R)-2-[(6-amino-1-oxohexan-2-yl)amino]-4-[6-(4-phenylpiperidine-1-yl)-1,2-benzoxazol-3-yl]butanoate as the probable binder which developed extensive conservative interactions despite the local pocket residues movements especially from kl ß-hairpin, the key structural unit for initiating conformational changes required for fusion transition. The electronic and hydrophobic potentials also indicated that butanoate molecule as the initial lead for envelope protein inhibitors.