Metabolomics-driven investigation of plant defense response against pest and pathogen attack.

The advancement of metabolomics has assisted in the identification of various bewildering characteristics of the biological system. Metabolomics is a standard approach, facilitating crucial aspects of system biology with absolute quantification of metabolites using minimum samples, based on liquid/gas chromatography, mass spectrometry and nuclear magnetic resonance. The metabolome profiling has narrowed the wide gaps of missing information and has enhanced the understanding of a wide spectrum of plant-environment interactions by highlighting the complex pathways regulating biochemical reactions and cellular physiology under a particular set of conditions. This high throughput technique also plays a prominent role in combined analyses of plant metabolomics and other omics datasets. Plant metabolomics has opened a wide paradigm of opportunities for developing stress-tolerant plants, ensuring better food quality and quantity. However, despite advantageous methods and databases, the technique has a few limitations, such as ineffective 3D capturing of metabolites, low comprehensiveness, and lack of cell-based sampling. In the future, an expansion of plant-pathogen and plant-pest response towards the metabolite architecture is necessary to understand the intricacies of plant defence against invaders, elucidation of metabolic pathway operational during defence and developing a direct correlation between metabolites and biotic stresses. Our aim is to provide an overview of metabolomics and its utilities for the identification of biomarkers or key metabolites associated with biotic stress, devising improved diagnostic methods to efficiently assess pest and pathogen attack and generating improved crop varieties with the help of combined application of analytical and molecular tools.

A simulation-based approach to target Zika virus RNA-dependent RNA polymerase with marine compounds for antiviral development.

Despite significant efforts, currently, there is no particular drug available to treat Zika virus (ZIKV) infection, highlighting the urgent need for effective therapeutic interventions. To identify putative inhibitors of the ZIKV RdRp protein's RNA binding function, the present study applied an extensive in-silico drug discovery methodology. The initial phase involved virtual screening using Lipinski's rule of five as a filter, ensuring the selection of molecules with favorable pharmacokinetic properties. This process yielded 238 compounds with promising docking scores, ranging from -6.0 to -7.48 kcal/mol, indicative of their potential binding affinity to the ZIKV RdRp. To refine the selection, these compounds underwent a re-docking process, comparing their binding energies with a reference molecule known for its inhibitory action against RdRp. Remarkably, five compounds, labeled CMNPD30598, CMNPD27464, CMNPD25971, CMNPD27444, and CMNPD16599, demonstrated superior re-docking energies compared to the reference, suggesting a stronger interaction with the RdRp allosteric site. Subsequent molecular dynamics (MD) simulations provided insights into the stability of these complexes over time, reinforcing their potential as RdRp inhibitors. Additionally, the calculation of free binding energies and principal component analysis (PCA) of the free energy landscape offered a deeper understanding of the binding dynamics and energetics. This study not only highlights the utility of marine fungi compounds in antiviral drug discovery but also showcases the power of computational tools in identifying novel therapeutics. The identified compounds represent promising candidates for further experimental validation and development as ZIKV RdRp inhibitors.Communicated by Ramaswamy H. Sarma.

Targeting neuroblastoma by small-molecule inhibitors of human ALYREF protein: mechanistic insights using molecular dynamics simulations.

Neuroblastoma is a tumour of the sympathetic nervous system mainly prevalent in children. Many strategies have been employed to target several drug-targetable proteins for the clinical management of neuroblastoma. However, the heterogeneous nature of neuroblastoma presents serious challenges in drug development for its treatment. Albeit numerous medications have been developed to target various signalling pathways in neuroblastoma, the redundant nature of the tumour pathways makes its suppression unsuccessful. Recently, the quest for neuroblastoma therapy resulted in the identification of human ALYREF, a nuclear protein that plays an essential role in tumour growth and progression. Therefore, this study used the structure-based drug discovery method to identify the putative inhibitors targeting ALYREF for the Neuroblastoma treatment. Herein, a library of 119 blood-brain barrier crossing small molecules from the ChEMBL database was downloaded and docked against the predicted binding pocket of the human ALYREF protein. Based on docking scores, the top four compounds were considered for intermolecular interactions and molecular dynamics simulation analysis, which revealed CHEMBL3752986 and CHEMBL3753744 with substantial affinity and stability with the ALYREF. These results were further supported by binding free energies and essential dynamics analysis of the respective complexes. Hence, this study advocates the sorted compounds targeting ALYREF for further in vitro and in vivo assessment to develop a drug against neuroblastoma.Communicated by Ramaswamy H. Sarma.

Comprehensive and evolutionary analysis of Spodoptera litura-inducible Cytochrome P450 monooxygenase gene family in Glycine max elucidate their role in defense.

Plants being sessile organisms and lacking both circulating phagocytic cells and somatic adaptive immune response, have thrived on various defense mechanisms to fend off insect pests and invasion of pathogens. CYP450s are the versatile enzymes, which thwart plants against insect pests by ubiquitous biosynthesis of phytohormones, antioxidants, and secondary metabolites, utilizing them as feeding deterrents and direct toxins. Therefore, a comprehensive analysis of biotic stress-responsive CYPs from Glycine max was performed to ascertain their function against S. litura-infestation. Phylogenetic analysis and evolutionary studies on conserved domains and motifs disclosed the evolutionary correspondence of these GmCYPs with already characterized members of the CYP450 superfamily and close relatedness to Medicago truncatula. These GmCYPs were mapped on 13 chromosomes; they possess 1-8 exons; they have evolved due to duplication and are localized in endoplasmic reticulumn. Further, identification of methyl-jasmonate, salicylic acid, defense responsive and flavonoid biosynthesis regulating cis-acting elements, their interaction with biotic stress regulating proteins and their differential expression in diverse types of tissues, and during herbivory, depicted their responsiveness to biotic stress. Three-dimensional homology modelling of GmCYPs, docking with heme cofactor required for their catalytic activity and enzyme-substrate interactions were performed to understand the functional mechanism of their action. Moreover, to gain insight into their involvement in plant defense, gene expression analysis was evaluated, which revealed differential expression of 11 GmCYPs upon S. litura-infestation, 12 GmCYPs on wounding while foliar spray of ethylene, methyl-jasmonate and salicylic acid differentially regulated 11 GmCYPs, 6 GmCYPs, and 10 GmCYPs respectively. Our study comprehensively analysed the underlying mechanism of GmCYPs function during S. litura-infestation, which can be further utilized for functional characterization to develop new strategies for enhancing soybean resistance to insect pests.

Identification and validation of a small molecule targeting ROR1 for the treatment of triple negative breast cancer.

Introduction: Breast cancer is the most common cancer in women, with roughly 10-15% of new cases classified as triple-negative breast cancer (TNBC). Traditional chemotherapies are often toxic to normal cells. Therefore, it is important to discover new anticancer compounds that target TNBC while causing minimal damage to normal cells. Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is an oncofetal protein overexpressed in numerous human malignancies, including TNBC. This study investigated potential small molecules targeting ROR1. Methodology: Using AutoDock Vina and Glide, we screened 70,000 chemicals for our investigation. We obtained 10 representative compounds via consensus voting, deleting structural alerts, and clustering. After manual assessment, compounds 2 and 4 were chosen for MD simulation and cell viability experiment. Compound 4 showed promising results in the viability assay, which led us to move further with the apoptosis assay and immunoblotting. Results: Compound 4 (CID1261330) had docking scores of -6.635 and -10.8. It fits into the pocket and shows interactions with GLU64, ASP174, and PHE93. Its RMSD fluctuates around 0.20 nm and forms two stable H-bonds indicating compound 4 stability. It inhibits cell proliferation in MDA-MB-231, HCC1937, and HCC1395 cell lines, with IC50 values of approximately 2 µM to 10 µM, respectively. Compound 4 did not kill non-malignant epithelial breast cells MCF-10A (IC50 > 27 µM). These results were confirmed by the significant number of apoptotic cells in MDA-MB-231 cells (47.6%) but not in MCF-10A cells (7.3%). Immunoblot analysis provided additional support in the same direction. Discussion: These findings collectively suggest that compound 4 has the potential to effectively eliminate TNBC cells while causing minimal harm to normal breast cells. The promising outcomes of this study lay the groundwork for further testing of compound 4 in other malignancies characterized by ROR1 upregulation, serving as a proof-of-concept for its broader applicability.

Silibinin: an inhibitor for a high-expressed BCL-2A1/BFL1 protein, linked with poor prognosis in breast cancer.

Breast cancer (BC) accounts for 30% of all diagnosed cases of cancer in women and remains a leading cause of cancer-related deaths among women worldwide. The current study looks for a protein from the anti-apoptotic/pro-survival BCL-2 family whose overexpression reduces survivability in BC patients and a potential inhibitor for the protein. We found BCL-2A1/BFL1 protein with high expression linked to low survivability in BC. The protein shows prognosis in 8 out of 29 categories, whereas no other family member manifests this property. Out of 7379 compounds, three small molecules (CHEMBL9509, CHEMBL2104550 and CHEMBL3545011) form an H-bond with BCL-2A1/BFL1 protein's unique residue Cys55. Of the three small molecules, we found CHEMBL9509 (Silibinin) to be a potent inhibitor. The compound forms a stable H-bond with the residue Cys55 with the lowest binding energy compared to the other two compounds. It remains stable in the BH3 binding region for more than 100 ns, whereas the other two detach from the region. Additionally, the compound is found to be better than Venetoclax and Nematoclax. We firmly believe in the compound CHEMBL9509 potency to halt BC's progression by inhibiting the BCL-2A1/BFL1 protein, increasing patients' survivability.Communicated by Ramaswamy H. Sarma.

Deciphering mitogen activated protein kinase pathway activated during insect attack in Nicotiana attenuata.

Plant yields are compromised due to abiotic and biotic stresses. A crucial biotic stress instigated by insect attack, is a major concern that limits crop production. To overcome the deleterious effect of herbivory, pesticides are used but long-term usage of pesticides can be harmful to the environment and human health. Understanding the plants' inherent defense mechanism by interpreting the interaction pattern of defense-related proteins and signalling components and manipulating them to strengthen defense status, is one of the alternative approaches of green biotechnology. During insect attack, host plants initiate innumerable signalling pathways to activate defense response; Mitogen Activated Protein Kinase (MAPK) Pathway is a crucial component of signalling pathway that regulate the expression of downstream defense-related genes. MAPK pathway has three components: MAPKKK, MAPKK and MAPK. Earlier studies have shown participation of SIPK and WIPK (MAPKs) as well as MEK2 (MAPKK) during insect infestation and its association with plant defense. However, information on the third component and elucidation of the complete MAPK pathway are still elusive. Therefore, this study aims to identify the unknown component and decipher MAPK pathway in Nicotiana attenuata involved in plant defense against herbivory by identifying herbivory-inducible MAPKKKs and and their interaction with known partners of the MAPK pathway by docking and MD simulation. The possible pathway was predicted to be MAPKKK Na12134/Na04522-MEK2-SIPK/WIPK. Further, validation of the above interaction by in vitro and in vivo methods is highly recommended.Communicated by Ramaswamy H. Sarma.

A comprehensive investigation of lipid-transfer proteins from Cicer arietinum disentangles their role in plant defense against Helicoverpa armigera-infestation.

Lipid Transfer Proteins (LTPs) play a crucial role in synthesizing lipid barrier polymers and are involved in defense signaling during pest and pathogen attacks. Although LTPs are conserved with multifaceted roles in plants, these are not yet identified and characterized in Cicer arietinum. In this study, a genome-wide analysis of LTPs was executed and their physiochemical properties, biochemical function, gene structure analysis, chromosomal localization, promoter analysis, gene duplication, and evolutionary analysis were performed using in silico tools. Furthermore, tissue-specific expression analysis and gene expression analysis during pest attack was also conducted for the LTPs. A total of 48 LTPs were identified and named as CaLTPs. They were predicted to be small unstable proteins with "Glycolipid transfer protein" and "Alpha-Amylase Inhibitors, Lipid Transfer and Seed Storage" domains, that are translocated to the extracellular region. CaLTPs were predicted to possess 3-4 introns and were located on all the eight chromosomes of chickpea with half of the CaLTPs being localized on chromosomes 4, 5, and 6, and found to be closely related to LTPs of Arabidopsis thaliana and Medicago trancatula. Gene duplication and synteny analysis revealed that most of the CaLTPs have evolved due to tandem or segmental gene duplication and were subjected to purifying selection during evolution. The promoters of CaLTPs had development-related, phytohormone-responsive, and abiotic and biotic stress-related cis-acting elements. A few CaLTP transcripts exhibited differential expression in diverse tissue types, while others showed no/very low expression. Out of 20 jasmonate-regulated CaLTPs, 14 exhibited differential expression patterns during Helicoverpa armigera-infestation, indicating their role in plant defense response. This study identified and characterized CaLTPs from an important legume, C. arietinum, and indicated their involvement in plant defense against H. armigera-infestation, which can be further utilized to explore lipid signaling during plant-pest interaction and pest management.

Breast Cancer Therapeutics and Hippo Signaling Pathway: Novel MicroRNA-Gene-Protein Interaction Networks.

The Hippo signaling pathway is a master regulator of development, cell proliferation, and apoptosis in particular, and it plays an important role in tissue regeneration, controlling organ size, and cancer suppression. Dysregulation of the Hippo signaling pathway has been implicated in breast cancer, a highly prevalent cancer affecting 1 out of every 15 women worldwide. While the Hippo signaling pathway inhibitors are available, they are suboptimal, for example, due to chemoresistance, mutation, and signal leakage. Inadequate knowledge about the Hippo pathway connections and their regulators limits our ability to uncover novel molecular targets for drug development. We report here novel microRNA (miRNA)-gene and protein-protein interaction networks in the Hippo signaling pathway. We employed the GSE miRNA dataset for the present study. The GSE57897 dataset was normalized and searched for differentially expressed miRNAs, and their targets were searched using the miRWalk2.0 tool. From the upregulated miRNAs, we observed that the hsa-miR-205-5p forms the biggest cluster and targets four genes involved in the Hippo signaling pathway. Interestingly, we found a novel connection between two Hippo signaling pathway proteins, angiomotin (AMOT) and mothers against decapentaplegic homolog 4 (SMAD4). From the downregulated miRNAs, hsa-miR-16-5p, hsa-miR-7g-5p, hsa-miR-141-3p, hsa-miR-103a-3p, hsa-miR-21-5p, and hsa-miR-200c-3p, target genes were present in the pathway. We found that PTEN, EP300, and BTRC were important cancer-inhibiting proteins, form hubs, and their genes interact with downregulating miRNAs. We suggest that targeting proteins from these newly unraveled networks in the Hippo signaling pathway and further research on the interaction of hub-forming cancer-inhibiting proteins can open up new avenues for next-generation breast cancer therapeutics.

Comparative transcriptome analysis of Zea mays upon mechanical wounding.

BACKGROUND: Mechanical wounding (MW) is mainly caused due to high wind, sand, heavy rains and insect infestation, leading to damage to crop plants and an increase in the incidences of pathogen infection. Plants respond to MW by altering expression of genes, proteins, and metabolites that help them to cope up with the stress. METHODS AND RESULTS: In order to characterize maize transcriptome in response to mechanical wounding, a microarray analysis was executed. The study revealed 407 differentially expressed genes (DEGs) (134 upregulated and 273 downregulated). The upregulated genes were engaged in protein synthesis, transcription regulation, phytohormone signaling-mediated by salicylic acid, auxin, jasmonates, biotic and abiotic stress including bacterial, insect, salt and endoplasmic reticulum stress, cellular transport, on the other hand downregulated genes were involved in primary metabolism, developmental processes, protein modification, catalytic activity, DNA repair pathways, and cell cycle. CONCLUSION: The transcriptome data present here can be further utilized for understanding inducible transcriptional response during mechanical injury and their purpose in biotic and abiotic stress tolerance. Furthermore, future study concentrating on the functional characterization of the selected key genes (Bowman Bird trypsin inhibitor, NBS-LRR-like protein, Receptor-like protein kinase-like, probable LRR receptor-like ser/thr-protein kinase, Cytochrome P450 84A1, leucoanthocyanidin dioxygenase, jasmonate O-methyltransferase) and utilizing them for genetic engineering for crop improvement is strongly recommended.

Regulation of the regulators: Transcription factors controlling biosynthesis of plant secondary metabolites during biotic stresses and their regulation by miRNAs.

Biotic stresses threaten to destabilize global food security and cause major losses to crop yield worldwide. In response to pest and pathogen attacks, plants trigger many adaptive cellular, morphological, physiological, and metabolic changes. One of the crucial stress-induced adaptive responses is the synthesis and accumulation of plant secondary metabolites (PSMs). PSMs mitigate the adverse effects of stress by maintaining the normal physiological and metabolic functioning of the plants, thereby providing stress tolerance. This differential production of PSMs is tightly orchestrated by master regulatory elements, Transcription factors (TFs) express differentially or undergo transcriptional and translational modifications during stress conditions and influence the production of PSMs. Amongst others, microRNAs, a class of small, non-coding RNA molecules that regulate gene expression post-transcriptionally, also play a vital role in controlling the expression of many such TFs. The present review summarizes the role of stress-inducible TFs in synthesizing and accumulating secondary metabolites and also highlights how miRNAs fine-tune the differential expression of various stress-responsive transcription factors during biotic stress.

Silicon nanoparticles: Synthesis, uptake and their role in mitigation of biotic stress.

In the current scenario of global warming and climate change, plants face many biotic stresses, which restrain growth, development and productivity. Nanotechnology is gaining precedence over other means to deal with biotic and abiotic constraints for sustainable agriculture. One of nature's most beneficial metalloids, silicon (Si) shows ameliorative effect against environmental challenges. Silicon/Silica nanoparticles (Si/SiO2NPs) have gained special attention due to their significant chemical and optoelectronic capabilities. Its mesoporous nature, easy availability and least biological toxicity has made it very attractive to researchers. Si/SiO2NPs can be synthesised by chemical, physical and biological methods and supplied to plants by foliar, soil, or seed priming. Upon uptake and translocation, Si/SiO2NPs reach their destined cells and cause optimum growth, development and tolerance against environmental stresses as well as pest attack and pathogen infection. Using Si/SiO2NPs as a supplement can be an eco-friendly and cost-effective option for sustainable agriculture as they facilitate the delivery of nutrients, assist plants to mitigate biotic stress and enhances plant resistance. This review aims to present an overview of the methods of formulation of Si/SiO2NPs, their application, uptake, translocation and emphasize the role of Si/SiO2NPs in boosting growth and development of plants as well as their conventional advantage as fertilizers with special consideration on their mitigating effects towards biotic stress.

Herbivory-inducible lipid-transfer proteins (LTPs) of Cicer arietinum as potential human allergens.

Lipid-transfer proteins (LTPs) are lipid-binding small proteins, ubiquitously distributed amongst plant kingdom. Apart from their involvement in plant defense, it has also been discovered that they induce allergic reactions in humans. A plethora of LTPs have been identified in vegetables, fruits, pollens, nuts, and latex, among which Pru p 3, a LTP allergen from peach fruit, is extensively studied and exhibits cross-reactivity with potential allergens from different species. In Cicer arietinum, a family of LTPs (CaLTPs) has been identified and their importance in plant defense during Helicoverpa armigera-infestation has been recognized. However, the determination of the allergenicity potential of CaLTPs has not been attempted. In this study, we aim to decipher the allergenicity potential of defense-related CaLTPs. The allergenicity potential prediction, and identification of B-cell epitope binding regions showed that the CaLTPs had conserved domains and B-cell epitopes in the same regions as Prup3 (a marker allergen for LTPs). Using molecular docking and simulations, we observed that the CaLTPs successfully interacted with the Immunoglobin E(IgE)with docking energies ranging from -315.5 to -268.4 and the structures were stabilized within 10 ns of simulation. Through this study, we intend to embellish our present knowledge and understanding of the sensitization and allergenicity potential of CaLTPs.Communicated by Ramaswamy H. Sarma.

Deciphering the role of miRNA in reprogramming plant responses to drought stress.

Drought is the most prevalent environmental stress that affects plants' growth, development, and crop productivity. However, plants have evolved adaptive mechanisms to respond to the harmful effects of drought. They reprogram their: transcriptome, proteome, and metabolome that alter their cellular and physiological processes and establish cellular homeostasis. One of the crucial regulatory processes that govern this reprogramming is post-transcriptional regulation by microRNAs (miRNAs). miRNAs are small non-coding RNAs, involved in the downregulation of the target mRNA via translation inhibition/mRNA degradation/miRNA-mediated mRNA decay/ribosome drop off/DNA methylation. Many drought-inducible miRNAs have been identified and characterized in plants. Their main targets are regulatory genes that influence growth, development, osmotic stress tolerance, antioxidant defense, phytohormone-mediated signaling, and delayed senescence during drought stress. Overexpression of drought-responsive miRNAs (Osa-miR535, miR160, miR408, Osa-miR393, Osa-miR319, and Gma-miR394) in certain plants has led to tolerance against drought stress indicating their vital role in stress mitigation. Similarly, knock down (miR166/miR398c) or deletion (miR169 and miR827) of miRNAs has also resulted in tolerance to drought stress. Likewise, engineered Arabidopsis plants with miR165, miR166 using short tandem target mimic strategy, exhibited drought tolerance. Since miRNAs regulate the expression of an array of drought-responsive genes, they can act as prospective targets for genetic manipulations to enhance drought tolerance in crops and achieve sustainable agriculture. Further investigations toward functional characterization of diverse miRNAs, and understanding stress-responses regulated by these miRNAs and their utilization in biotechnological applications is highly recommended.

Dhurrin: A naturally occurring phytochemical as a weapon against insect herbivores.

Dhurrin, a cyanogenic glucoside, is a plant defensive chemical synthesized from aliphatic amino acids and consists of ß-d-glucopyranose linked to α-hydroxy nitrile. It is catabolized by the consecutive action of hydroxynitrilase and ß-glucosidase to release hydrogen cyanide on tissue disruption during herbivory. These phytoanticipins are widely distributed across various monocot and dicot plants such as Sorghum, Macadamia, Ostrya sp., and many other plant species with ornamental, pharmaceutical, medicinal, and food value. Although repellent properties of dhurrin against herbivores are often reported, less is known about its distribution, metabolism, mode of action against insects, and application for pest control. Herein, we highlight recent updates on dhurrin distribution, biosynthesis, and catabolism along with the cyanide detoxification pathway. Additionally, this article focuses on biological activities of dhurrin against various herbivores and opportunities to explore the utilization of dhurrin as a natural pest control agent and a substitute for chemically synthesized pesticides.

Comparative analysis of web-based programs for single amino acid substitutions in proteins.

Single amino-acid substitution in a protein affects its structure and function. These changes are the primary reasons for the advent of many complex diseases. Analyzing single point mutations in a protein is crucial to see their impact and to understand the disease mechanism. This has given many biophysical resources, including databases and web-based tools to explore the effects of mutations on the structure and function of human proteins. For a given mutation, each tool provides a score-based outcomes which indicate deleterious probability. In recent years, developments in existing programs and the introduction of new prediction algorithms have transformed the state-of-the-art protein mutation analysis. In this study, we have performed a systematic study of the most commonly used mutational analysis programs (10 sequence-based and 5 structure-based) to compare their prediction efficiency. We have carried out extensive mutational analyses using these tools for previously known pathogenic single point mutations of five different proteins. These analyses suggested that sequence-based tools, PolyPhen2, PROVEAN, and PMut, and structure-based web tool, mCSM have a better prediction accuracy. This study indicates that the employment of more than one program based on different approaches should significantly improve the prediction power of the available methods.

How to Cope with the Challenges of Environmental Stresses in the Era of Global Climate Change: An Update on ROS Stave off in Plants.

With the advent of human civilization and anthropogenic activities in the shade of urbanization and global climate change, plants are exposed to a complex set of abiotic stresses. These stresses affect plants' growth, development, and yield and cause enormous crop losses worldwide. In this alarming scenario of global climate conditions, plants respond to such stresses through a highly balanced and finely tuned interaction between signaling molecules. The abiotic stresses initiate the quick release of reactive oxygen species (ROS) as toxic by-products of altered aerobic metabolism during different stress conditions at the cellular level. ROS includes both free oxygen radicals {superoxide (O2•-) and hydroxyl (OH-)} as well as non-radicals [hydrogen peroxide (H2O2) and singlet oxygen (1O2)]. ROS can be generated and scavenged in different cell organelles and cytoplasm depending on the type of stimulus. At high concentrations, ROS cause lipid peroxidation, DNA damage, protein oxidation, and necrosis, but at low to moderate concentrations, they play a crucial role as secondary messengers in intracellular signaling cascades. Because of their concentration-dependent dual role, a huge number of molecules tightly control the level of ROS in cells. The plants have evolved antioxidants and scavenging machinery equipped with different enzymes to maintain the equilibrium between the production and detoxification of ROS generated during stress. In this present article, we have focused on current insights on generation and scavenging of ROS during abiotic stresses. Moreover, the article will act as a knowledge base for new and pivotal studies on ROS generation and scavenging.

In silico validation of novel inhibitors of malarial aspartyl protease, plasmepsin V and antimalarial efficacy prediction.

Plasmepsin V (Plm V) is an essential aspartic protease required for survival of the malaria parasite, Plasmodium falciparum (Pf). Plm V is required for cleaving the PEXEL motifs of many Pf proteins and its inhibition leads to a knockout effect, indicating its suitability as potential drug target. To decipher new inhibitors of PfPlm V, molecular docking of four HIV-1 protease inhibitors active against PfPlmV was performed on Glide module of Schrödinger suite that supported saquinavir as a lead drug, and therefore, selected as a control. Saquinavir contains an important hydroxyethylamine (HEA) pharmacophore, which was utilized as backbone coupled with piperazine scaffold to build new library of compounds. Newly designed HEA compounds were screened virtually against Plm V. Molecular docking led to a few hits (1 and 3) with higher docking score over the control drug. Notably, compound 1 showed the highest docking score (-11.90 kcal/mol) and XP Gscore (-11.948 kcal/mol). The Prime MMGBSA binding free energy for compound 1 (-60.88 kcal/mol) and 3 (-50.96 kcal/mol) was higher than saquinavir (-37.51 kcal/mol). The binding free energy for the last frame of molecular dynamic simulation supported compound 1 (-92.88 kcal/mol) as potent inhibitor of PfPlm V over saquinavir (-72.77 kcal/mol), and thus, deserves experimental validations in culture and subsequently in animal models.Communicated by Ramaswamy H. Sarma.

Role of nanoparticles in crop improvement and abiotic stress management.

Nanoparticles (NPs) possess specific physical and chemical features and they are capable enough to cross cellular barriers and show their effect on living organisms. Their capability to cross cellular barriers have been noticed for their application not only in medicine, electronics, chemical and physical sciences, but also in agriculture. In agriculture, nanotechnology can help to improve the growth and crop productivity by the use of various nanoscale products such as nanofertilizers, nanoherbicides, nanofungicides, nanopesticides etc. An optimized concentration of NPs can be administered by incubation of seeds, roots, pollen, isolated cells and protoplast, foliar spraying, irrigation with NPs, direct injection, hydroponic treatment and delivery by biolistics. Once NPs come in contact with plant cells, they are uptaken by plasmodesmatal or endocytosed pathways and translocated via apoplastic and / symplastic routes. Once beneficial NPs reach different parts of plants, they boost photosynthetic rate, biomass measure, chlorophyll content, sugar level, buildup of osmolytes and antioxidants. NPs also improve nitrogen metabolism, enhance chlorophyll as well as protein content and upregulate the expression of abiotic- and biotic stress-related genes. Herein, we review the state of art of different modes of application, uptake, transport and prospective beneficial role of NPs in stress management and crop improvement.