Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel corona virus that causes corona virus disease 2019 (COVID-19). The COVID-19 rapidly spread across the nations with high mortality rate even as very little is known to contain the virus at present. In the current study, we report novel natural metabolites namely, ursolic acid, carvacrol and oleanolic acid as the potential inhibitors against main protease (M pro) of COVID-19 by using integrated molecular modeling approaches. From a combination of molecular docking and molecular dynamic (MD) simulations, we found three ligands bound to protease during 50 ns of MD simulations. Furthermore, the molecular mechanic/generalized/ Born/Poisson-Boltzmann surface area (MM/G/P/BSA) free energy calculations showed that these chemical molecules have stable and favourable energies causing strong binding with binding site of M pro protein. All these three molecules, namely, ursolic acid, carvacrol and oleanolic acid, have passed the ADME (Absorption, Distribution, Metabolism, and Excretion) property as well as Lipinski's rule of five. The study provides a basic foundation and suggests that the three phytochemicals, viz. ursolic acid, carvacrol and oleanolic acid could serve as potential inhibitors in regulating the M pro protein's function and controlling viral replication.

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Pseudomonas aeruginosa is a leading opportunistic pathogen and its expanding drug resistance is a growing menace to public health. Its ubiquitous nature and multiple resistance mechanisms make it a difficult target for antimicrobial chemotherapy and require a fresh approach for developing new antimicrobial agents against it. The broad-spectrum antibacterial effects of silver nanoparticles (SNPs) make them an excellent candidate for use in the medical field. However, attempts made to check their potency against extensively drug-resistant (XDR) microbes are meager. This study describes the biosynthesis and biostabilization of SNPs by Helicteres isora aqueous fruit extract and their characterization by ultraviolet-visible spectroscopy, transmission electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. Majority of SNPs synthesized were of 8--20-nm size. SNPs exhibited dose-dependent antibacterial activities against four XDR P. aeruginosa (XDR-PA) clinical isolates as revealed by growth curves, with a minimum inhibitory concentration of 300 μg/ml. The SNPs exhibited antimicrobial activity against all strains, with maximum zone of inhibition (16.4 mm) in XRD-PA-2 at 1000 μg/ml. Amongst four strains, their susceptibilities to SNPs were in the following order: XDR-PA-2 > XDR-PA-4 > XDR-PA-3 > XDR-PA-1. The exposure of bacterial cells to 300 μg/ml SNPs resulted into a substantial leakage of reducing sugars and proteins, inactivation of respiratory chain dehydrogenases, and eventual cell death. SNPs also induced lipid peroxidation, a possible underlying factor to membrane porosity. The effects were more pronounced in XDR-PA-2 which may be correlated with its higher susceptibility to SNPs. These results are indicative of SNP-induced turbulence of membranous permeability as an important causal factor in XDR-PA growth inhibition and death.

RWP-RKs represent a small family of transcription factors (TFs) that are unique to plants and function particularly under conditions of nitrogen starvation. These RWP-RKs have been classified in two sub-families, NLPs (NIN-like proteins) and RKDs (RWP-RK domain proteins). NLPs regulate tissue-specific expression of genes involved in nitrogen use efficiency (NUE) and RKDs regulate expression of genes involved in gametogenesis/embryogenesis. During the present study, using in silico approach, 37 wheat RWP-RK genes were identified, which included 18 TaNLPs (2865 to 7340 bp with 4/5 exons), distributed on 15 chromosomes from 5 homoeologous groups (with two genes each on 4B,4D and 5A) and 19 TaRKDs (1064 to 5768 bp with 1 to 6 exons) distributed on 12 chromosomes from 4 homoeologous groups (except groups 1, 4 and 5); 2–3 splice variants were also available in 9 of the 37 genes. Sixteen (16) of these genes also carried 24 SSRs (simple sequence repeats), while 11 genes had targets for 13 different miRNAs. At the protein level, MD simulation analysis suggested their interaction with nitrate-ions. Significant differences were observed in the expression of only two (TaNLP1 and TaNLP2) of the nine representative genes that were used for in silico expression analysis under varying levels of N at post-anthesis stage (data for other genes was not available for in silico expression analysis). Differences in expression were also observed during qRT-PCR, when expression of four representative genes (TaNLP2, TaNLP7, TaRKD6 and TaRKD9) was examined in roots and shoots of seedlings (under different conditions of N supply) in two contrasting genotypes which differed in NUE (C306 with low NUE and HUW468 with high NUE). These four genes for qRT-PCR were selected on the basis of previous literature, level of homology and the level of expression (in silico study). In particular, the TaNLP7 gene showed significant up-regulation in the roots and shoots of HUW468 (with higher NUE) during N-starvation; this gene has already been characterized in Arabidopsis and tobacco, and is known to be involved in nitrate-signal transduction pathway.

Antimicrobial resistance (AMR) is a serious concern in pathogenic bacteria. As a new approach to addressing AMR, we report here the green synthesis of vanillin capped gold nanoparticles (VAuNPs) using the popular flavouring molecule vanillin (C 8 H 8 O 3 ) as a reducing and capping agent. Physicochemical characterization revealed that the synthesised VAuNPs were stable and crystalline in nature. VAuNPs were non-bactericidal even at high concentration (>2000 μg/ml). The antibiotic potentiation activity was studied in combination with seven widely used antibiotics against extremely drug resistant (XDR) Pseudomonas aeruginosa . Major reductions in minimum inhibitory concentrations (MIC, 10–14-folds) of the antibiotics meropenem (10 fold) and trimethoprim (14 fold) were observed in the presence of VAuNPs (50 μg/ml). Furthermore, it was found that VAuNPs in combination with meropenem or trimethoprim provided 1.5–3-fold better potentiation effects than that of vanillin alone. Use of an ethidium bromide agar cart wheel assay indicated that VAuNPs can block the activity of efflux pumps. High reduction in the MIC of antibiotics was therefore attributed to the efflux pump repression activity of VAuNPs. Further, RT-qPCR of clinically relevant MexAB-OprM efflux pump components showed down-regulation in mexB and OprM transcripts in VAuNPs treated P. aeruginosa clinical isolates. Our results reveal that VAuNPs impart susceptibility to the last line antibiotics meropenem, trimethoprim and few widely used antibiotics in XDR P. aeruginosa clinical isolates that display resistance to these antibiotics. Therefore, this study indicate the ability of VAuNPs and vanillin to be used as antibiotic adjuvants for inhibiting bacterial efflux pumps to potentiate antibiotics for addressing AMR problem affecting human health and environment.

Introduction: In recent years, natural antioxidants have seen an unprecedented importance and demand in bio-pharmaceuticals, nutraceuticals besides their use as food additives. Antioxidants act as potential prophylactic and therapeutic agents against various diseases caused by free-radicals. Plants offer tremendous source of antioxidants and are therefore being evaluated for their potentials. Eulophia nuda is an important medicinal plant used by local healers in India; however its antioxidant properties have not yet been investigated. Methods: Aqueous (AqE), methanol (ME), aqueousemethanol (AqME) and acetone (AE) extracts of shade dried tubers were obtained and were concentrated in vacuo. Total phenols, flavonoids, ascorbic acid and carotenoids were estimated from all extracts using standard methods. Antioxidant activities of extracts were determined by total antioxidant activity, FRAP, ABTS, DPPH, and OH radical scavenging assays besides lipid peroxidation inhibition. Extracts were evaluated for protection of Fenton's reagent induced DNA damage. Results: The results confirmed the plant as a rich source of phenols, flavonoids, vitamin C and carotenoids. Among four extracts, AqME showed highest antioxidant activities as evidenced by maximum scavenging of ABTS (98%), DPPH (87%), and OH radicals (99%) at 1 mg ml À1 concentration and showed maximal inhibition of lipid peroxidation. All extracts protected the DNA from hydroxyl-radical-induced damage. Again, AqME was proved to be best in providing protection to DNA against damage caused by freeradicals. Conclusion: The results provides scientific basis for its traditional usage as natural antioxidant and phytotherapeutic agent. The plant possesses high amount of phenolic compounds and showed a broadspectrum antioxidant properties including DNA protection.

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Abstract:Medicinal plants are the main natural pools for the primary health care system, ethno-medicine, as well as traditional Indian system of several medicines. Uttarakhand also known as 'Herbal State', is a rich source of medicinal plants and traditional medicinal knowledge. A great deal of information about medicinal plants of Uttarakhand is scattered in different forms. Although many medicinal plant databases are available, currently there is no cohesive manually curated database of medicinal plants widely distributed in Uttarakhand state. A comprehensive database has been developed, known as the Uttarakhand Medicinal Plants Database (UMPDB). UMPDB provides extensive information on botanical name, common name, taxonomy, genomic taxonomy id, habit, habitat, location in Uttarakhand, part use, medicinal use, genomic information (including number of nucleotides, proteins, ESTs), chemical information, and scientific literature. Annotated medicinal plants integrated in the current version of the database were collected from the existing books, databases, and available literature. The current version of UMPDB contains the 1127 records of medicinal plants which belong to 153 plant families distributed across 13 districts of Uttarakhand. The primary goal of developing this database is to provide traditional, genomic, and chemical descriptions of the medicinal plants exclusively found in various regions of Uttarakhand. We anticipate that embedded information in the database would help users to readily obtain desired information.