A review of artificial intelligence-assisted omics techniques in plant defense: current trends and future directions.

Plants intricately deploy defense systems to counter diverse biotic and abiotic stresses. Omics technologies, spanning genomics, transcriptomics, proteomics, and metabolomics, have revolutionized the exploration of plant defense mechanisms, unraveling molecular intricacies in response to various stressors. However, the complexity and scale of omics data necessitate sophisticated analytical tools for meaningful insights. This review delves into the application of artificial intelligence algorithms, particularly machine learning and deep learning, as promising approaches for deciphering complex omics data in plant defense research. The overview encompasses key omics techniques and addresses the challenges and limitations inherent in current AI-assisted omics approaches. Moreover, it contemplates potential future directions in this dynamic field. In summary, AI-assisted omics techniques present a robust toolkit, enabling a profound understanding of the molecular foundations of plant defense and paving the way for more effective crop protection strategies amidst climate change and emerging diseases.

In silico screening of phytoconstituents as potential anti-inflammatory agents targeting NF-κB p65: an approach to promote burn wound healing.

Chronic burn wounds are frequently characterised by a prolonged and dysregulated inflammatory phase that is mediated by over-activation of NF-κB p65. Synthetic wound healing drugs used for treatment of inflammation are primarily associated with several shortcomings which reduce their therapeutic index. In this scenario, phytoconstituents that exhibit multifaceted biological activities including anti-inflammatory effects have emerged as a promising therapeutic alternative. However, identification and isolation of phytoconstituents from medicinal herbs is a cumbersome method that is linked to profound uncertainty. Hence, present study aimed to identify prospective phytoconstituents as inhibitors of RHD of NF-κB p65 by utilizing in silico approach. Virtual screening of 2821 phytoconstituents was performed against protein model. Out of 2821 phytoconstituents, 162 phytoconstituents displayed a higher binding affinity (≤ -8.0 kcal/mol). These 162 phytoconstituents were subjected to ADMET predictions, and 15 of them were found to satisfy Lipinski's rule of five and showed favorable pharmacokinetic properties. Among these 15 phytoconstituents, 5 phytoconstituents with high docking scores i.e. silibinin, bismurrayaquinone A, withafastuosin B, yuccagenin, (+)-catechin 3-gallate were selected for molecular dynamics (MD) simulation analysis. Results of MD simulation indicated that withafastuosin B, (+)-catechin 3-gallate and yuccagenin produced a compact and stable complex with protein without significant variations in conformation. Relative binding energy analysis of best hit molecules indicate that withafastuosin B, and (+)-catechin 3-gallate exhibit high binding affinity with target protein among other lead molecules. Findings of study suggest that these phytoconstituents could serve as promising anti-inflammatory agents for treatment of burn wounds by inhibiting the RHD of NF-κB p65.Communicated by Ramaswamy H. Sarma.

In silico mutation of aromatic with aliphatic amino acid residues in Clostridium perfringens epsilon toxin (ETX) reduces its binding efficiency to Caprine Myelin and lymphocyte (MAL) protein receptors.

Enterotoxaemia (ET) is a severe disease that affects domestic ruminants, including sheep and goats, and is caused by Clostridium perfringens type B and D strains. The disease is characterized by the production of Epsilon toxin (ETX), which has a significant impact on the farming industry due to its high lethality. The binding of ETX to the host cell receptor is crucial, but still poorly understood. Therefore, the structural features of goat Myelin and lymphocytic (MAL) protein were investigated and defined in this study. We induced the mutations in aromatic amino acid residues of ETX and substituted them with aliphatic residues at domains I and II. Subsequently, protein-protein interactions (PPI) were performed between ETX (wild)-MAL and ETX (mutated)-MAL protein predicting the domain sites of ETX structure. Further, molecular dynamics (MD) simulation studies were performed for both complexes to investigate the dynamic behavior of the proteins. The binding efficiency between 'ETX (wild)-MAL protein' and 'ETX (mutated)-MAL protein complex' interactions were compared and showed that the former had stronger interactions and binding efficiency due to the higher stability of the complex. The MD analysis showed destabilization and higher fluctuations in the PPI of the mutated heterodimeric ETX-MAL complex which is otherwise essential for its functional conformation. Such kind of interactions with mutated functional domains of ligands provided much-needed clarity in understanding the pre-pore complex formation of epsilon toxin with the MAL protein receptor of goats. The findings from this study would provide an impetus for designing a novel vaccine for Enterotoxaemia in goats.Communicated by Ramaswamy H. Sarma.

Unraveling the Aurora kinase A and Epstein-Barr nuclear antigen 1 axis in Epstein Barr virus associated gastric cancer.

Aurora kinase A (AURKA) is one of the crucial cell cycle regulators associated with gastric cancer. Here, we explored Epstein Barr Virus-induced gastric cancer progression through EBV protein EBNA1 with AURKA. We found that EBV infection enhanced cell proliferation and migration of AGS cells and upregulation of AURKA levels. AURKA knockdown markedly reduced the proliferation and migration of the AGS cells even with EBV infection. Moreover, MD-simulation data deciphered the probable connection between EBNA1 and AURKA. The in-vitro analysis through the transcript and protein expression showed that AURKA knockdown reduces the expression of EBNA1. Moreover, EBNA1 alone can enhance AURKA protein expression in AGS cells. Co-immunoprecipitation and NMR analysis between AURKA and EBNA1 depicts the interaction between two proteins. In addition, AURKA knockdown promotes apoptosis in EBV-infected AGS cells through cleavage of Caspase-3, -9, and PARP1. This study demonstrates that EBV oncogenic modulators EBNA1 possibly modulate AURKA in EBV-mediated gastric cancer progression.

MethSemble-6mA: an ensemble-based 6mA prediction server and its application on promoter region of LBD gene family in Poaceae.

The Lateral Organ Boundaries Domain (LBD) containing genes are a set of plant-specific transcription factors and are crucial for controlling both organ development and defense mechanisms as well as anthocyanin synthesis and nitrogen metabolism. It is imperative to understand how methylation regulates gene expression, through predicting methylation sites of their promoters particularly in major crop species. In this study, we developed a user-friendly prediction server for accurate prediction of 6mA sites by incorporating a robust feature set, viz., Binary Encoding of Mono-nucleotide DNA. Our model,MethSemble-6mA, outperformed other state-of-the-art tools in terms of accuracy (93.12%). Furthermore, we investigated the pattern of probable 6mA sites at the upstream promoter regions of the LBD-containing genes in Triticum aestivum and its allied species using the developed tool. On average, each selected species had four 6mA sites, and it was found that with speciation and due course of evolution in wheat, the frequency of methylation have reduced, and a few sites remain conserved. This obviously cues gene birth and gene expression alteration through methylation over time in a species and reflects functional conservation throughout evolution. Since DNA methylation is a vital event in almost all plant developmental processes (e.g., genomic imprinting and gametogenesis) along with other life processes, our findings on epigenetic regulation of LBD-containing genes have dynamic implications in basic and applied research. Additionally, MethSemble-6mA (http://cabgrid.res.in:5799/) will serve as a useful resource for a plant breeders who are interested to pursue epigenetic-based crop improvement research.

Insilico generation of novel ligands for the inhibition of SARS-CoV-2 main protease (3CLpro) using deep learning.

The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CLpro). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinski's rule of 5, high binding affinity (highest binding affinity: -9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CLpro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19.

Underutilized legumes: nutrient status and advanced breeding approaches for qualitative and quantitative enhancement.

Underutilized/orphan legumes provide food and nutritional security to resource-poor rural populations during periods of drought and extreme hunger, thus, saving millions of lives. The Leguminaceae, which is the third largest flowering plant family, has approximately 650 genera and 20,000 species and are distributed globally. There are various protein-rich accessible and edible legumes, such as soybean, cowpea, and others; nevertheless, their consumption rate is far higher than production, owing to ever-increasing demand. The growing global urge to switch from an animal-based protein diet to a vegetarian-based protein diet has also accelerated their demand. In this context, underutilized legumes offer significant potential for food security, nutritional requirements, and agricultural development. Many of the known legumes like Mucuna spp., Canavalia spp., Sesbania spp., Phaseolus spp., and others are reported to contain comparable amounts of protein, essential amino acids, polyunsaturated fatty acids (PUFAs), dietary fiber, essential minerals and vitamins along with other bioactive compounds. Keeping this in mind, the current review focuses on the potential of discovering underutilized legumes as a source of food, feed and pharmaceutically valuable chemicals, in order to provide baseline data for addressing malnutrition-related problems and sustaining pulse needs across the globe. There is a scarcity of information about underutilized legumes and is restricted to specific geographical zones with local or traditional significance. Around 700 genera and 20,000 species remain for domestication, improvement, and mainstreaming. Significant efforts in research, breeding, and development are required to transform existing local landraces of carefully selected, promising crops into types with broad adaptability and economic viability. Different breeding efforts and the use of biotechnological methods such as micro-propagation, molecular markers research and genetic transformation for the development of underutilized crops are offered to popularize lesser-known legume crops and help farmers diversify their agricultural systems and boost their profitability.

In-silico study of protein-protein interactions in wheat blast using docking and molecular dynamics simulation approach.

Despite advancements in agricultural research and the introduction of modern biotechnological and farming techniques, food security remains a significant issue. Although the efforts of farmers to meet the demands of a growing population, many plant diseases caused by pathogens, through their effects on cell division and tissue growth, lead to the annual loss of countless food crops. The recently emerged wheat blast fungus Magnaporthe oryzae pathotype Triticum (MoT) poses a significant danger to worldwide wheat cultivation. The fungus is a highly varied lineage of the M. oryzae, responsible for causing rice blast disease. In spite of being a significant challenge to successful wheat production in South America since 1985, the underlying biology of the wheat blast pathogen is still not fully understood. The initial outbreak of the wheat blast in South Asia had a severe impact on wheat production, resulting in a complete loss of yield in affected fields. For the purpose of enhancing disease management, it's vital to acquire a comprehensive comprehension of the infection biology of the fungus and its interaction with wheat plants on molecular levels. Host-pathogen protein interactions (HPIs) have the potential to reveal the pathogens' mechanism for overcoming the host organism. The current study delves into the interactions between the host plant wheat and MoT through protein-protein interactions, molecular docking, and 100 ns molecular dynamic simulations. This research uncovers the structural and functional basis of these proteins, leading to improved plant health and production.Communicated by Ramaswamy H. Sarma.

Targeting Epstein-Barr Virus dUTPase, an Immunomodulatory Protein Using Antiviral, Anti-Inflammatory, and Neuroprotective Phytochemicals.

Although primary infection of Epstein-Barr virus is generally non-lethal, viral reactivation is often associated with fatal outcomes. Regardless, there is no FDA-approved treatment available for this omnipresent viral infection. The current investigation targets viral maintenance and reactivation by inhibiting the functioning of viral deoxyuridine-triphosphatase (dUTPase) using phytochemicals. The EBV-dUTPase is essential for maintaining nucleotide balance and thus, plays a vital role in the viral replication cycle. Additionally, the protein has shown neuroinflammatory effects on the host. To selectively target the protein and possibly alter its activity, we utilized a virtual screening approach and screened 45 phytochemicals reported to have antiviral, anti-inflammatory, and neuroprotective properties. The analysis revealed several phytochemicals bound to the target protein with high affinity. In-silico ADMET and Lipinski's rule analysis predicted favorable druggability of Dehydroevodiamine (DHE) among all the phytochemicals. Further, we corroborated our findings by molecular dynamic simulation and binding affinity estimation. Our outcomes ascertained a stable binding of DHE to EBV-dUTPase primarily through electrostatic interactions. We identified that the protein-ligand binding involves the region around His71, previously reported as a potent drug target site. Conclusively, the phytochemical DHE showed a promising future as a drug development candidate against EBV-dUTPase.

Biocomputational Assessment of Natural Compounds as a Potent Inhibitor to Quorum Sensors in Ralstonia solanacearum.

Ralstonia solanacearum is among the most damaging bacterial phytopathogens with a wide number of hosts and a broad geographic distribution worldwide. The pathway of phenotype conversion (Phc) is operated by quorum-sensing signals and modulated through the (R)-methyl 3-hydroxypalmitate (3-OH PAME) in R. solanacearum. However, the molecular structures of the Phc pathway components are not yet established, and the structural consequences of 3-OH PAME on quorum sensing are not well studied. In this study, 3D structures of quorum-sensing proteins of the Phc pathway (PhcA and PhcR) were computationally modeled, followed by the virtual screening of the natural compounds library against the predicted active site residues of PhcA and PhcR proteins that could be employed in limiting signaling through 3-OH PAME. Two of the best scoring common ligands ZINC000014762512 and ZINC000011865192 for PhcA and PhcR were further analyzed utilizing orbital energies such as HOMO and LUMO, followed by molecular dynamics simulations of the complexes for 100 ns to determine the ligands binding stability. The findings indicate that ZINC000014762512 and ZINC000011865192 may be capable of inhibiting both PhcA and PhcR. We believe that, after further validation, these compounds may have the potential to disrupt bacterial quorum sensing and thus control this devastating phytopathogenic bacterial pathogen.

Combatting insects mediated biotic stress through plant associated endophytic entomopathogenic fungi in horticultural crops.

Horticultural production is a vital catalyst for economic growth, yet insect infestations reduce horticultural crop yield and quality. Pesticides and other pest control methods are used during planting to eliminate pests that cause direct and indirect losses. In such situations, endophytic entomo-pathogenic fungi (EEPF) can act as a potential tools for biological control. They protect plants by boosting growth, nutrition, morpho-physiology and salt or iron tolerance. Antixenosis, antibiosis and plant tolerance change insect performance and preferences. EEPF- plant colonisation slows herbivore development, food consumption, oviposition and larval survival. EEPF changes plant physio-chemical properties like volatile emission profile and secondary metabolite production to regulate insect pest defences. EEPF produces chitinases, laccases, amylases, and cellulases for plant defence. Recent studies focused on EEPF species' significance, isolation, identification and field application. Realizing their full potential is difficult due to insufficient mass production, storage stability and formulation. Genetic-molecular and bioinformatics can help to build EEPF-based biological control systems. Metagenomics helps study microbial EEPF taxonomy and function. Multi-omics and system biology can decode EEPF interactions with host plants and microorganisms. NGS (Next Generation Sequencing), comparative genomics, proteomics, transcriptomics, metabolomics, metatranscriptomics and microarrays are used to evaluate plant-EEPF relationships. IPM requires understanding the abiotic and biotic elements that influence plant-EEPF interaction and the physiological mechanisms of EEPF colonisation. Due to restricted research, there are hundreds of unexplored EEPFs, providing an urgent need to uncover and analyse them.