Casein kinase-1 alpha (CK1α) is a multifunctional protein kinase that belongs to the serine/threonine kinases of the CK1α family. It is involved in various signaling pathways associated with chromosome segregation, cell metabolism, cell cycle progression, apoptosis, autophagy, etc. It has been known to involve in the progression of many diseases, including cancer, neurodegeneration, obesity, and behavioral disorders. The elevated expression of CK1α in diseased conditions facilitates its selective targeting for therapeutic management. Here, we have performed virtual screening of phytoconstituents from the IMPPAT database seeking potential inhibitors of CK1α. First, a cluster of compounds was retrieved based on physicochemical parameters following Lipinski’s rules and PAINS filter. Further, high-affinity hits against CK1α were obtained based on their binding affinity score. Furthermore, the ADMET, PAINS, and PASS evaluation was carried out to select more potent hits. Finally, following the interaction analysis, we elucidated three phytoconstituents, Semiglabrinol, Curcusone_A, and Liriodenine, posturing considerable affinity and specificity towards the CK1α binding pocket. The result was further evaluated by molecular dynamics (MD) simulations, dynamical cross-correlation matrix (DCCM), and principal components analysis (PCA), which revealed that binding of the selected compounds, especially Semiglabrinol, stabilizes CK1α and leads to fewer conformational fluctuations. The MM-PBSA analysis suggested an appreciable binding affinity of all three compounds toward CK1α.

Increasing the yield of extraction of bioactive compounds from plants is of high importance. Grape stems are widely discarded during the wine-making process, despite their high content in many valuable compounds. The aim of this work was to examine whether the use of pulsed electric field (PEF) treatment of the stems could increase the yield of polyphenol and volatile compounds in the extracts. For this reason, a relatively low-energy consuming PEF process was employed (low-electric field strength, 1 kV/cm) for a short time (30 min) at the grape stems. In addition, the effect of different solvents during this pretreatment step was examined. With the use of Folin–Ciocalteu assay, the extracts were compared with the respective control samples (not pretreated with PEF). Moreover, extracts were prepared to assess whether changes occur to the volatile profile of the extracts. The results were conclusive that not only PEF can increase the yield of polyphenols (up to 35% increase recorded), but also that the solvent used during PEF pretreatment can affect the process. Furthermore, a 234% increase in the total content of volatile compounds was recorded, when PEF was used as a pretreatment step. Therefore, the combination of PEF and ultrasound-assisted extraction is highly promising to obtain grape stem extracts with a higher content of bioactive compounds.

Scientists have discovered many ways to treat bacteria, viruses, and parasites in aquaculture; however, there is still an impossibility in finding a permanent solution for all types of diseases. In that case, the CRISPR-Cas genome-editing technique can be the potential solution to preventing diseases for aquaculture sustainability. CRISPR-Cas is cheaper, easier, and more precise than the other existing genome-editing technologies and can be used as a new disease treatment tool to solve the far-reaching challenges in aquaculture. This technique may now be employed in novel ways, such as modifying a single nucleotide base or tagging a location in the DNA with a fluorescent protein. This review paper provides an informative discussion on adopting CRISPR technology in aquaculture disease management. Starting with the basic knowledge of CRISPR technology and phages, this study highlights the development of RNA-guided immunity to combat the Chilodonella protozoan group and nervous necrosis virus (NNV) in marine finfish. Additionally, we highlight the immunological application of CRISPR-Cas against bacterial diseases in channel catfish and the white spot syndrome virus (WSSV) in shrimp. In addition, the review summarizes a synthesis of bioinformatics tools used for CRISPR-Cas sgRNA design, and acceptable solutions are discussed, considering the limitations.

Carbonic anhydrase II (CAII) is one of the zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide, leading to the formation of bicarbonate and proton. CAII plays a significant role in health and disease. For example, CAII helps to maintain eye pressure while regulating the pH of the tumor microenvironment, and by extension, contributing to cancer progression. Owing to its remarkable role in cancer, visual health, and other human diseases, CAII can serve as an attractive therapeutic target. We report an original study based on high-throughput virtual screening of natural compounds from the ZINC database in search of potential inhibitors of CAII. We selected the hits based on the physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, pan-assay interference compound (PAINS) patterns, and interaction analysis. Importantly, two natural compounds were identified, ZINC08918123 and ZINC00952700, bearing considerable affinity and specific interactions to the residues of the CAII-binding pocket with well-organized conformational fitting compatibility. We investigated the conformational dynamics of CAII in complex with the identified compounds through molecular dynamics simulation, which revealed the formation of a stable complex preserved throughout the 100 ns trajectories. The stability of the protein/ligand complexes is maintained by significant numbers of noncovalent interactions throughout the simulations. In conclusion, natural compounds identified in the present study specifically and computer-assisted drug design broadly offer a reliable resource and strategy to discover potential promising therapeutic inhibitors of CAII to cure various cancers and glaucoma after further experimental validation and clinical studies.

Irisin is a clinically significant protein playing a valuable role in regulating various diseases. Irisin attenuates synaptic and memory dysfunction, highlighting its importance in Alzheimer’s disease. On the other hand, Microtubule Affinity Regulating Kinase 4 (MARK4) is associated with various cancer types, uncontrolled neuronal migrations, and disrupted microtubule dynamics. In addition, MARK4 has been explored as a potential drug target for cancer and Alzheimer’s disease therapy. Here, we studied the binding and subsequent inhibition of MARK4 by irisin. Irisin binds to MARK4 with an admirable affinity (K = 0.8 × 10⁷ M⁻¹), subsequently inhibiting its activity (IC₅₀ = 2.71 µm). In vitro studies were further validated by docking and simulations. Molecular docking revealed several hydrogen bonds between irisin and MARK4, including critical residues, Lys38, Val40, and Ser134. Furthermore, the molecular dynamic simulation showed that the binding of irisin resulted in enhanced stability of MARK4. This study provides a rationale to use irisin as a therapeutic agent to treat MARK4-associated diseases.