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

Genome-Wide Identification and Characterization of Trihelix Gene Family in Asian and African <i>Vigna</i> Species

Trihelix transcription factors play a crucial role in varied stress responses as well as in the growth and development of plants. The role of trihelix transcription factors in the non-shattering phenotype in domesticated rice is known. The Vigna group of crops has different degrees of shattering phenotypes in different species. To understand the evolutionary conservation or divergence of the trihelix gene family in important Vigna species here, the genome-wide identification and characterization of the trihelix gene family in four Vigna species including the cowpea (Vigna unguiculata), mung bean (V. radiata), adzuki bean (V. angularis) and rice bean (V. umbellata) was performed. A total of 39, 35, 41 and 50 trihelix genes were identified in the cowpea, mung bean, adzuki bean and rice bean, respectively. The trihelix genes in each of the four Vigna species were classified into five subgroups: GT, GTγ, SH4, S1P1 and GTδ. The members of each subgroup shared similar patterns of gene structure and motif across the four species. The cross-species positional relationships of the cowpea, adzuki bean and mung bean vis-a-vis rice trihelix genes were studied. Further, the Ka/Ks ratio for the trihelix genes in the four Vigna species indicated the purifying or stabilizing selection of the family. The gene expression analysis of the trihelix gene family in the cowpea showed that most of the genes express in at least some of the seed and/or pod developmental stages, although at varying degrees. Based on detailed bioinformatic analysis, a potential target for gene editing towards a possible non-shattering phenotype in the four important Vigna crops was discussed

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Not AvailableEnterotoxaemia (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 pro duction 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 per formed 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 pro tein’ and ‘ETX (mutated)-MAL protein complex’ interactions were compared and showed that the for mer 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 interac tions 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.ICA

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

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