Lactoperoxidase (LPO) is a heme-containing mammalian enzyme that is found in the extracellular fluids of animals including plasma, saliva, airway epithelial and nasal lining fluids, milk, tears, and gastric juices. LPO uses hydrogen peroxide (H2O2) to convert substrates into oxidized products. Previous structural studies have shown that H2O2, CO, and CN are bound to LPO at the distal heme cavity by coordinating with heme iron. The structure of the complex of LPO with NO shows that NO also binds to LPO at the distal heme cavity and forms a coordinate linkage with heme iron. The structure shows that the nitrogen atom of NO is linked to heme iron at a distance of 1.97 while the oxygen atom is attached to the Nε2 atom of His109 at a distance of 2.23 Å. On the other hand, N atom of NO is located with an interatomic distance of 3.25 Å allowing a hydrogen-bonding interaction with the Nε2 atom of Gln105. A comparison of the bindings of NO, CO, CN, and H2O2 in coordination with heme iron indicates stereochemical compatibility of the distal heme cavity for the binding of diatomic molecules. However, notable differences are observed in their orientations in the distal heme cavity indicating functional differences. The bindings of NO, CO, and CN by coordinating with heme iron result in the inhibition of LPO while the binding of H2O2 to heme iron produces an intermediate of LPO known as Compound I.

The rise of antimicrobial resistance has positioned ESKAPE pathogens as a serious global health threat, primarily due to the limitations and frequent failures of current treatment options. This growing risk has spurred the scientific community to seek innovative antibiotic therapies and improved oversight strategies. This review aims to provide a comprehensive overview of the origins and resistance mechanisms of ESKAPE pathogens, while also exploring next-generation treatment strategies for these infections. In addition, it will address both traditional and novel approaches to combating antibiotic resistance, offering insights into potential new therapeutic avenues. Emerging research underscores the urgency of developing new antimicrobial agents and strategies to overcome resistance, highlighting the need for novel drug classes and combination therapies. Advances in genomic technologies and a deeper understanding of microbial pathogenesis are crucial in identifying effective treatments. Integrating precision medicine and personalized approaches could enhance therapeutic efficacy. The review also emphasizes the importance of global collaboration in surveillance and stewardship, as well as policy reforms, enhanced diagnostic tools, and public awareness initiatives, to address resistance on a worldwide scale.

Background: Type-III Pantothenate kinase from the multi drug resistant bacteria, Acinetobacter baumannii (AbPanK) catalyzes the first step of the essential Coenzyme A biosynthesis pathway. AbPanK is an attractive drug target against the bacteria since it is an essential enzyme and its structure is significantly different from the human PanK. Methods: AbPanK was cloned, expressed, purified and crystallized. A good quality single crystal was used for X-ray intensity data collection. Dynamic light scattering was done for calculating the hydrodynamic radii and its oligomeric nature in the solution. Binding studies of this protein with its two substrates, Pantothenate and ATP were done using spectrofluorometer. Results: Our results indicated that AbPanK shows a strong affinity with pantothenate with dissociation constant of 1.2 x 10-8 M and moderate affinity towards ATP of 3.7x 10-3 M. This fact was further substantiated by the calculations of Km of both substrates using kinase assay kit. Dynamic light scattering studies have shown that it exists as homogenous solution with hydrodynamic radii corresponding to the molecular weight of 29.55 kDa. A low-resolution X-ray intensity data set was collected, which shows that AbPank crystallizes in P2 space group with cell dimensions of a= 165 Å, b= 260 Å, and, c= 197 Å and α= 90.0, β= 113.60, γ= 90.0. Discussion: Recombinant Pantothenate kinase from Acinetobacter baumannii was purified to homogeneity and crystallized. The enzyme exhibits very low sequence identity (28%) to other corresponding enzymes. Conclusion: The recombinant enzyme was active and its binding affinities with its substrates pantothenate and ATP have been studied. This information would be very useful while designing the inhibitors of this enzyme in order to fight bacterial infections associated to this pathogen.

Mucormycosis is a deadly infection which is caused by fungi of the order Mucorales including species belonging to the genus Rhizopus, Mucor, Mycocladus, Rhizomucor, Cunninghamella, and Apophysomyces. Despite antifungal therapy and surgical procedures, the mortality rate of this disease is about 90-100% which is exceptionally high. The hypersensitivity of patients with raised available serum iron indicates that the Mucorales are able to use host iron as a critical factor of virulence. This is because iron happens to be a crucial element playing its role in the growth of cells and development. In this review, we have described Lactoferrin (Lf) as a potential iron-chelator. Lf is a naturally occurring glycoprotein which is expressed in most of the biological fluids. Moreover, Lf possesses exclusive anti-inflammatory effects along with several anti-fungal effects that could prove to be helpful to the pathological physiology of inexorable mucormycosis cases. This literature summarises the biological insights into the Lf being considered as a potential fungistatic agent and an immune regulator. The review also proposes that unique potential of Lf as an iron-chelator can be exploited as the adjunct treatment for mucormycosis infection.

The recent outbreak of the SARS-CoV-2 virus leading to the disease COVID 19, a global pandemic has resulted in an unprecedented loss of life and economy worldwide. Hence, there is an urgent need to discover effective drugs to control this pandemic. NSP16 is a methyltransferase that methylates the ribose 2 '-O position of the viral nucleotide. Taking advantage of the recently solved structure of NSP16 with its inhibitor, S-Adenosylmethionine, we have virtually screened FDA approved drugs, drug candidates and natural compounds. The compounds with the best docking scores were subjected to molecular dynamics simulations followed by binding free energy calculations using the MM-PBSA method. The known drugs which were identified as potential inhibitors of NSP16 from SARS-CoV-2 included DB02498, DB03909, DB03186, Galuteolin, ZINC000029416466, ZINC000026985532, and ZINC000085537017. DB02498 (Carba-nicotinamide-adenine-dinucleotide) is an approved drug which has been used since the late 1960s in intravenous form to significantly lessen withdrawal symptoms from a variety of drugs and alcohol addicts and it has the best MM-PBSA binding free energy of-12.83 +/- 0.52 kcal/mol. The second best inhibitor, Galuteolin is a natural compound that inhibits tyrosinase enzyme with MM-PBSA binding free energy value of -11.21 +/- 0.47 kcal/mol. Detailed ligand and protein interactions were analyzed and common residues across SARS-CoV, SARS-CoV-2, and MERS-CoV were identified. We propose Carba-nicotinamide-adenine-dinucleotide and Galuteolin as the potential inhibitors of NSP16. The results in this study can be used for the treatment of COVID-19 and can also form the basis of rational drug design against NSP16 of SARS-CoV-2.

Phosphopantetheine adenylyl transferase catalyzes a rate limiting penultimate step of the multistep reaction which produces coenzyme A (CoA) as a final product. CoA is required as an essential cofactor in a number of metabolic reactions. Therefore inhibiting the function of this enzyme will lead to cell death in bacteria. Acinetobacter baumannii is multi drug resistant pathogen and causes infections in immunocompromised patients. AbPPAT has been cloned, expressed, purified and crystallized and structures of two complexes of AbPPAT with dephospho coenzyme A (dPCoA) and coenzyme A (CoA) have been determined. Both dPCoA and CoA molecules are observed in the substrate binding site of AbPPAT. A comparison with the structures of the complexes of PPAT from other species shows that the orientations of dPCoA are identical in all the structures. On the other hand, as observed from the structures of the complexes of CoA with PPAT, the orientations of CoA are found to differ considerably. This shows that the substrates occupy identical positions in the substrate binding sites of enzymes whereas the positions of inhibitors may differ. The binding studies carried out using fluorescence method and surface plasmon resonance techniques showed that binding affinity of CoA towards AbPPAT is nearly three times higher than that of dPCoA.

The use of untapped plant genetic resources of wheat (Triticum spp.) can enhance its productivity. In the present study, we characterized 22,416 accessions of three different species of wheat conserved in the Indian National Genebank using 23 qualitative and 12 quantitative traits to develop a core set. These accessions were highly diverse on the basis of range, coefficient of variation, and Shannon-Weaver diversity index. Initial grouping was done on the bases of species and origin, and thereafter, agromorphological data were used to develop core sets for each species group using the heuristic approach with PowerCore. Finally, a composite core set was constituted comprising 2,226 accessions, which included 1,779 accessions of bread wheat (T. aestivum L.), 394 of durum wheat [T. turgidum L. subsp. durum (Desf.) van Slageren], and 53 of emmer wheat [T. dicoccon Schrank; syn. T. turgidum L. subsp. dicoccon (Schrank) Thell]. The core set was validated under field conditions. Also, the coincidence rate of range (CR) (bread wheat, 85.78%; durum wheat, 87.52%; and emmer wheat, 95.34%) and variable rate of the coefficient of variation (VR) (bread wheat, 174.9%; durum wheat, 136.5%; and emmer wheat, 105.81%) were more than the threshold values of 80 and 100%, respectively. The phenotypic correlations among different traits attributable to coadapted gene complexes and total variation shown by principal components in the entire set were also mostly preserved in the core set. The composite wheat core and the trait-specific germplasm sets identified would serve as valuable resources for global wheat improvement programs.

The recent outbreak of the SARS-CoV-2 virus leading to the disease COVID 19 has become a global pandemic that is spreading rapidly and has caused a global health emergency. Hence, there is an urgent need of the hour to discover effective drugs to control the pandemic caused by this virus. Under such conditions, it would be imperative to repurpose already known drugs which could be a quick and effective alternative to discovering new drugs. The main protease (Mpro) of SARS-COV-2 is an attractive drug target because of its essential role in the processing of the majority of the non-structural proteins which are translated from viral RNA. Herein, we report the high-throughput virtual screening and molecular docking studies to search for the best potential inhibitors against Mpro from FDA approved drugs available in the ZINC database as well as the natural compounds from the Specs database. Our studies have identified six potential inhibitors of Mpro enzyme, out of which four are commercially available FDA approved drugs (Cobicistat, Iopromide, Cangrelor, and Fortovase) and two are from Specs database of natural compounds (Hopeaphenol and Cyclosieversiodide-A). While Cobicistat and Fortovase are known as HIV drugs, Iopromide is a contrast agent and Cangrelor is an anti-platelet drug. Furthermore, molecular dynamic (MD) simulations using GROMACS were performed to calculate the stability of the top-ranked compounds in the active site of Mpro. After extensive computational studies, we propose that Cobicistat and Hopeaphenol show potential to be excellent drugs that can form the basis of treating COVID-19 disease.Communicated by Ramaswamy H. Sarma.

In mammalian cells, human 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate-limiting endoplasmic reticulum (ER) bonded enzyme, plays a central role in the cholesterol homeostasis via the negative feedback mechanism. The present study indicates that the interactions of novel peptides with the catalytic domain of HMGCR, provides an alternative therapeutic candidate for reducing cholesterol. The potential natural origin of HMGCR peptide inhibitors were filtered from the peptide library using the molecular docking, which revealed three strong candidates for inhibition. This information was used for synthesizing peptides, which were evaluated for inhibition against HMGCR. The stronger docking interactions were confirmed by experimental dissociation constant (K-D) values of 9.1 x 10(-9) M, 1.4 x 10(-8) M and 1.2 x 10(-8) M for peptides NALEPDNRIESEGG (Pep-1), NALEPDNRIES (Pep-2) and PFVKSEPIPETNNE (Pep-3) respectively. The immunological based interactions show a strong evidence of peptide-HMGCR complexes. The LDL uptake showed enhancements after treatments with peptides in the extracellular environment of HepG2 cells, which was further, corroborated through increase in the immunofluorescence signal of the localized LDL-R protein expression on the cell membrane. The results showed that the mRNA and protein expression of transcription factors were significantly up-regulated showing regulation of cholesterol biosynthesis in peptide treated HepG2 cells. The binding of transcription factors, sterol regulatory element (SRE) and cAMP-response element (CRE) on HMGCR promotor further confirms the cholesterol biosynthesis regulation. All the above results suggested a key role of peptide/s in alleviating cholesterol accumulation in tissue via inhibition of rate-limiting HMGCR enzyme.

Phosphopantetheine adenylyltransferase (PPAT, EC. 2.7.7.3) catalyzes an essential step in the reaction that transfers an adenylyl group from adenosine tri phosphate (ATP) to 4'-phosphopantetheine (pPant) yielding 3'-dephospho-coenzyme A (dPCoA) and pyrophosphate (PP) in the coenzyme A (CoA) biosynthesis pathway. The enzyme PPAT from Acinetobacter baumannii (AbPPAT) was cloned, expressed and purified. The binding studies of AbPPAT were carried out with two compounds, tri-sodium citrate (TSC) and L-ascorbic acid (LAA, vitamin-C) using fluorescence spectroscopic (FS) and surface Plasmon resonance (SPR) methods. Both methods provided similar values of dissociation constants for TSC and LAA which were of the order of 10(-8) M and 10(-5) M respectively. The computer aided docking studies indicated fewer interactions of IAA with AbPPAT as compared to those of TSC. The freshly purified samples of AbPPAT were crystallized. The crystals of AbPPAT were soaked in the solutions containing TSC and LAA. However, the crystals of the complex of AbPPAT with LAA did not diffract well and hence the structure of the complex of AbPPAT with LAA could not be determined. On the other hand, the crystals of the complex of AbPPAT with TSC diffracted well and the structure was determined at 1.76 angstrom resolution. It showed that TSC bound to AbPPAT at the ATP binding site and formed several intermolecular contacts including 12 hydrogen bonds. The results of binding studies for both TSC and LAA and the structure of the complex of AbPPAT with TSC clearly indicated a potential role of TSC and LAA as antibacterial agents.

Assessment of genetic diversity and its application for wheat breeding resulted in enhanced and sustainable production and productivity. One hundred and two spring wheat cultivars were evaluated for 19 agro-morphological and physiological traits under late sown conditions for two years. The cluster analysis revealed significant genetic variability among wheat cultivars that shows the excellent opportunity to bring about improvement through hybridizing the selected genotypes present in distant clusters. The data was further subjected to PCA (principal component analysis) and genotype by trait biplot analysis. The first 2 principal components accounted for 33.8% of the total variation. Phenological traits and growing degree days had major contribution towards heat tolerance as indicated by principal component analysis. Correlation analysis revealed that grain yield was positively associated with biological yield and harvest index. Promising cultivars were identified for terminal heat tolerance that can be adapted for growing under the late sown condition and further used for breeding improved climate-resilient wheat cultivars and genomics study. DOI.org/ 10.25174/2249-4065/2019/89261

Chickpea wilt caused by F. oxysporum f. sp. ciceri is one of the most important seed and soil-borne disease in India. The study on association of the pathogen with chickpea seeds showed that the viable mycelium fragments, micro and macro-conidia of the pathogen were present on the seed surface of all susceptible and two resistant varieties/ germplasms in seed washing test. The pathogen was recovered from the untreated and sodium hypochlorite treated seeds of all susceptible varieties/ germplasms in the range of 10.67–18.67 and 5.33–11.33 per cent, respectively in standard blotter method and 8.67–17.00 and 5.00–10.67 per cent, respectively in agar plate method, whereas the seeds of resistant varieties RSG-895 and Phule G-5 also carried the pathogen in untreated and sodium hypochlorite treated seeds. The recovery of pathogen was ranged from 10.0–20.0 per cent from the seed coat, 2.0–8.0 per cent from cotyledons and 2.0–6.0 per cent from embryonal axis of the susceptible varieties/germplasms. Whereas resistant variety RSG-895 carried the pathogen to an extent of 4.0 per cent from seed coat only. The pre-emergence infection of the pathogen was recorded by 6.0–14.0 per cent in different susceptible varieties/ germplasms and 4.0 per cent in resistant varieties during seedling symptom test. The pathogen was survived for 10–15 months in susceptible and 3–5 months in resistant varieties/ germplasms seeds. The pre and post-emergence losses due to the pathogen were ranged from 7.0–12.0 per cent and 6.0–10.0 per cent, respectively in susceptible varieties/ germplasms under field conditions in poly bags. The typical wilt symptoms have developed after 18–22 days of sowing and the average seed infection and seed transmission ratio was 6.08:1 under field conditions in susceptible varieties/ germplasms.

Traditional cultivars and primitive landraces of maize ( Zea mays L.) are invaluable treasure for humankind. These need to be collected, evaluated, conserved and utilized for increasing agricultural production and quality enhancement. Based on extensive survey, 58 diverse maize accessions were collected from Nagaland state of the North Eastern Himalayan region during year 2011. These collections were evaluated under two different agro-ecological regions located at New Delhi and Shillong using twelve quantitative variables during kharif 2012 and 2013 and nine qualitative traits. Significant variability was observed for the traits studied. The trait mean performance and variability were compared for both the environments and superior collections were identified. This study clearly demonstrated that despite environment-specific adaptations, several accessions are capable of showing high adaptability at region outside their habitat and could be utilized for diversifying the pools and deriving inbred lines with diverse features.

Wheat is the most important cereal crop and staple diet for more than one third of the world population and contributes more calories and protein to the world diet than any other cereal crop. In view of global climate change drought stress is becoming major constraints for the productivity of wheat and hence the breeding for drought tolerance is gaining more importance. More accurate and precise phenotyping of genetic resources is the demand of the new generation quantitative geneticists and plant breeders as this is the most critical research area which will lead to identification of trait specific donor germplasm. In the present study, Wheat germplasm accessions (1483 acc.) were evaluated at Issapur farm in Augmented Block Design with four checks based on morpho-physiological parameters. Irrigation was provided at Crown root initiation stage (CRI) and afterwards moisture deficit was maintained throughout the crop duration. There was wide variability in wheat germplasm for the phonological, agronomical and physiological traits. This experiment identified correlated traits responsible for high grain yield under rainfed conditionsuch as biological yield, harvest index, days to maturity, spike length, spikelets per spike, grains per spike, cholorophyll content, grain weight and 1000 grain weight. Based on stepwise multiple regression analysis, major role of prediction on yield was found through biological yield, including harvest index, grain weight spikelets per spike and chlorophyll content. Based on predictor variables, accessions were selected and will be further validated under controlled condition and will be used for introgression purpose in the background of elite varieties to enhance yield and its stability under moisture stress environments.

Purple blotch of onion caused by Alternaria porri is an economically important disease. The field trials were conducted during three crop seasons in order to study the effect of surfactant on the efficacy of fungicides because the use of fungicides for the control of purple blotch of onion is less promising due to the waxy and smooth leaf surface, which does not allow the fungicides to spread and adhere properly on the leaves. Chlorothalonil 75 WP (1.5 g/l) and mancozeb 75 (2.0 g/l) when sprayed along with surfactant (0.5 ml/l) showed minimum per cent disease index (5.38 and 7.96%, respectively) and disease incidence (11.80 and 15.47%, respectively) at 15 days after third spray in comparison to chlorothalonil and mancozeb alone where the disease index was 8.93 and 11.52%, respectively, and disease incidence was 15.92 and 20.38%, respectively. The results also indicated that the efficacy of fungicides was significantly increased by adding surfactant from 23.69 to 39.75 and 19.87 to 25.88% in minimizing disease index and disease incidence, respectively, in different treatments when compared with the fungicides without surfactant. Both chlorothalonil and mancozeb along with surfactant showed minimum disease severity (9.72 and 12.36%, respectively) at 15 days after third spray and highest bulb yield (237.70 and 231.96 q/ha, respectively) as compared to both the fungicides sprayed alone. The per cent increase in bulb yield over control ranged from 5.57 to 27.60 in different treatments. The fungicides along with surfactant reduced the per cent disease severity (16.15–24.12) and increased the bulb yield (5.31–9.81%) in different treatments when compared with the fungicides without surfactant. The study clearly demonstrated the potential of surfactant to improve the efficacy of fungicides against purple blotch of onion.

Plant genetic resources, the source of genetic diversity provides a broad genetic foundation for plant breeding and genetic research, however, large germplasm resources are difficult to preserve, evaluate and use. Construction of core and mini core collections is an efficient method for managing genetic resources and undertaking intensive surveys of natural variation, including the phenotyping of complex traits and genotyping of DNA polymorphisms allowing more efficient utilization of genetic resources. A mega characterization and evaluation programme of the entire cultivated gene pool of wheat conserved in the National Genebank, India was undertaken. Wheat accessions with limited seed quantity, were multiplied in the off-season nursery at IARI Regional Station, Wellington during rainy season 2011 and the entire set of 22,469 wheat accessions were characterized and evaluated at CCS HAU, Hisar, Haryana during winter season 2011–12 for 34 characters including 22 highly heritable qualitative, and 12 quantitative parameters. The core sets were developed using PowerCore Software with stepwise approach and grouping method and validated using Shannon-Diversity Index and summary statistics. Based on Shannon-Diversity index, PowerCore with stepwise approach was found better than PowerCore with grouping. The core set included 2,208 accessions comprising 1,770 T. aestivum, 386 T. durum, and 52 T. dicoccum accessions as a representative of the total diversity recorded in the wheat germplasm. The core set developed will be further validated at different agro-climatic conditions and will be utilized for development of mini core set to enhance the utilization by wheat researchers and development of climate resilient improved varieties.