Dengue virus is a positive-sense, single-stranded RNA virus of the Flaviviridae family. Aedes aegypti is the primary vector for transmitting dengue virus, spreading the tropical infectious illness. Currently, this virus is widespread in over 100 countries and is causing millions of new cases, which kill thousands of people each year as there is no medication available. Therefore, this study aims to identify a potential inhibitor from Dodonaea viscosa targeting the NS5 methyltransferase of the dengue virus through an in silico analysis and molecular docking approach. The NS5 methyltransferase is crucial in the host–pathogen interaction and the mechanism for this viral infection. However, Dodonaea viscosa has antiviral activity, and ligands were screened from different databases used for their preparation. Further, the molecular docking analysis was performed with the NS5 methyltransferase and screened ligands from Dodonaea viscosa. The analysis shows some promising compounds that can lead to therapeutic development, as they have high docking scores in comparison to the control used. An ADME analysis was performed for the bioactivity analysis of the selected ligands, and promising ligand profiles were found. Further, the identified potential inhibitor can be used for therapeutic development for dengue virus.

Introduction: Biomolecular structures play a role in the functioning of cells, controlling the processes that sustain life. This review embarks on a journey through recent advances in biomolecular structural studies, exploring the profound impact of cutting-edge techniques on unraveling the mysteries encoded within these molecular entities.

Methods: This review explores the range of techniques used to determine molecular structures. X ray crystallography, known for its atomic-level detail, is complemented by NMR spectroscopy, which provides insights into the behavior of molecules. The emergence of cryo electron microscopy has further expanded our abilities, allowing us to visualize assemblies of molecules with unprecedented clarity.

Result: Exciting breakthroughs in structural molecular studies have revealed transformative insights. From capturing the actions of enzymes to understanding how membrane proteins are arranged in space, these discoveries have revolutionized our understanding of biological processes. The results section highlights findings that emphasize the importance of these advancements.

Conclusion: The synthesis of knowledge is propelling biomolecular research into a new era. These groundbreaking revelations not contribute to our understanding but also have practical implications that can make a difference in various applications. This review concludes by emphasizing the pivotal role of biomolecular structures in shaping the trajectory of scientific inquiry, opening unprecedented avenues for exploration and application.

Aim:

• To pioneer an innovative in silico exploration of Zingiber officinalis for Rheumatoid Arthritis, employing virtual screening to discern the impact of its chemical constituents on the cyclo-oxygenase receptor.

Objectives:

• To identify ligands from Zingiber officinalis that exhibit high binding affinity towards the Cyclooxygenase receptor, aiming to contribute valuable insights into potential therapeutic agents for Rheumatoid Arthritis.
• To investigate the structural and dynamic aspects of the ligand-receptor interactions, providing a comprehensive understanding of the molecular mechanisms underlying the potential therapeutic effects against Rheumatoid Arthritis.
• To explore and characterize novel chemical entities within Zingiber officinalis, uncovering previously unrecognized candidates with promising binding affinity and therapeutic potential for Rheumatoid Arthritis.

Material and Methodology: Ginger-derived ligands were prepared by retrieving smiles from Pubchem, sketching 2D structures on Chemsketch, and optimizing results with Avogadro.

COX1 and COX2 receptors, obtained from a protein data bank, were visualized in PyMol and prepared using Autodock Vina. Virtual screening in PyRx involved ligand and macromolecule conversion, grid selection, and Molinspiration for property calculation, including acute oral toxicity prediction with Protox II.

Result and discussion: In silico studies revealed that all the synthesized molecules show good binding affinity toward the target protein ranging from −9.3 to −5.5.

Conclusion: The studies revealed that quercetin has higher binding as compared to the standard drug of rheumatoid arthritis i.e. ibuprofen. The ADME and toxicity studies also show positive results. Hence, this study has widened the scope of developing quercetin as a promising drug for rheumatoid arthritis

Glutathione could be a crucial cell molecule during plant–pathogen interplay response via its role in the direct control level of ROS. The proper regulation of ROS creates a line between susceptibility (with high damage to cell components) and host resistance in some plant–pathogen interactions. Therefore, we analyzed the role of glutathione forms (GSH/GSSG), as well as their cellular localization, in compatible and incompatible (HR reaction) potato cultivars infected with Potato virus Y ^NTN (PVY^NTN) during interaction in the symplast and apoplast with the use of microscopic and HPLC methods. Only the resistant potato plants characterized systemically increased glutathione production in both cell compartments, accompanied by a significant reduction in virus level. The susceptible potato plants were only able to induce glutathione at an early stage of infection; after that, glutathione levels were depleted, and virus concentration highly increased. This fact directly indicates that proper glutathione synthesis and concertation in the symplast and apoplast plays a role not only as anti-ROS protection but also as an antiviral factor in the infection of PVY^NTN. Whereas the apoplastic overpresence of GSSG and reduction in glutathione that occurred in the symplast are clear pro-viral factors for PVY^NTN. Therefore, supporting plant supplementation with glutathione could be a factor that changes/stimulates more resistance reactions to PVY^NTN infection.

Introduction

Prosequences are stretches of amino acid translated along with protein, but are often removed from the mature protein later through excision. This is known to assist the three-dimensional folding of their cognate protein, and also prevents precocious activation and proteolytic degradation. Prosequences are also termed intramolecular chaperones, and the whole stretch of an initially translated polypeptide is termed a preproprotein. Preproproteins have so far been reported in at least 690 organisms including eukaryotes, archaea, bacteria and viruses, with most of them being present as N-terminal prosequences. The unique role of prosequences can be exploited for protein engineering but this requires a detailed understanding of the role of prosquences in cognate protein folding. In this study, we tried to explore the structural effect of prosequences on their cognate preproprotein.

Method

Structural homologs of N-terminal prosequence-containing proteins were retrieved from PDB-based similarity and coverage criteria. The RING webserver was used for predicting prosequence and protein interacting sites. The possible binding pockets were predicted using CASTp. Known ligand-binding sites were explored through Pdbsum for verifying the ligand-binding residues.

Result

More than half of the structures studied showed involvement of prosequences with the cognate protein in terms of residue interactions. Fourteen of these structures werepredicted to have various binding site pockets. Out of these, seven structures were found to have prosequence residues involved in ligand binding.

Conclusion

Our studies show that, along with interacting with the cognate protein, N-terminal prosequences also participate in the formation of the binding pockets and interactions with ligands. Binding pockets formed in the protein part are also influenced by the prosequence, indicating their possible structural role imparting functional assistance.

Abstract

Introduction

Coronary artery disease (CAD) stands as the predominant global cause of mortality. Inflammation and the formation of atherosclerotic plaques constitute the primary pathological processes underlying CAD. Triggered by deposited lipids and compromised endothelial integrity, immune cells become activated and mobilized, instigating the initiation of plaque formation. MicroRNAs (miRNAs), 22-nucleotide-long non-coding RNA molecules, play an important role in regulating gene expression and present promising prospects for groundbreaking therapeutic and atherosclerosis in CAD.

Method

This investigation employed the Genetic Testing Registry (GTR), sourced from the National Center for Biotechnology Information (NCBI), for the identification of genes associated with coronary artery disease (CAD) featuring inflammation and atherosclerosis. Subsequently, gene enrichment analysis was conducted using ShinyGO, and predictions of conserved 8-mer miRNA targets were made utilizing three tools: TargetScan, miRWalk, and miRBase.

Results

Our data analysis unveiled a convergence of targeted miRNAs that were shared among genes associated with coronary artery disease (CAD), atherosclerosis, and inflammation. Noteworthy examples include miR-218-5p/96-5p/9-5p/20-5p/93-5p/106-5p/519-3p/506-3p/124-3p.2. These miRNAs exhibit the potential to play a pivotal role in the development of highly effective therapeutic approaches. Additionally, a distinct set of miRNAs, encompassing miR-19-3p/195-5p/29-3p/181-5p/27-3p/200a-3p/107/199-3p, was identified specifically for CAD and atherosclerosis. Similarly, miRNAs, such as miR-15-5p/424-5p/101-3p.2/30-5p/21-5p/124-3p.1, were selected for CAD and inflammation examination. Remarkably, these miRNAs were found to be common, targeting more than one gene in each pathological condition.

Conclusion

In conclusion, our findings highlights potential miRNAs that hold promise for enhancing therapeutic strategies against coronary artery disease (CAD) featuring inflammation and atherosclerosis. However, further research is warranted to assess their specific potential for each respective condition.

Chiral polymeric matrices with controlled sites of complementary-specific interactions are considered innovative substrates for the production of highly selective medicinal and pharmaceutical drugs. To solve this problem, information is necessary about the stereospecific features of the chemical substance used to obtain such biomaterials, including those under model conditions of intracellular communication and regulation.
This work considers the acid–base and chiro-optical properties of chiral biologically active salt complexes of chitosan and L-(D-)aspartic acid (CS∙L-(D-)AspA), which are promising for the design of stereofunctional biomaterials and pharmaceuticals. Special attention is paid to studies of the attenuation of optical anisotropy intensity during the process of model biomolecular condensation of L-menthol in the CS∙L-(D-)AspA medium.
It has been established that an increase in the [AspA]/[CS] molar ratio is accompanied by a decrease in pH and a decrease in the protonation degree of CS amino groups in salt complexes. Aqueous solutions of CS·L-(D-)AspA exhibit a positive and negative, respectively, Cotton effect in the UV region, which is the result of the π-π transition in the aminoaspartic chromophore. In the visible region, CS L- and D-aspartate is characterized by a left-handed rotation of the plane of polarization and monotonic dispersion of specific optical rotation. The phase separation of an ethanolic L-menthol solution in an aqueous CS∙L-(D-)AspA solution proceeds through the mechanism of selective extraction crystallization and combines two types of phase separation, namely, liquid–liquid and liquid–crystal. The “emulsion–dispersion” phase transition is accompanied by the disappearance of the birefringence effect in the condensed phase of the substance.
The results obtained show the promise of using CS∙L-(D-)AspA in studies of biomolecular condensation (the formation of highly labile associates of macromolecules due to liquid phase separation) and the biogenesis of membraneless organelles in physiological/pathological cellular processes.

Acknowledgment
This research was funded by the Russian Science Foundation No. 24-16-00172, https://rscf.ru/project/24-16-00172/.

Phycobiliproteins (PBPs) are fluorescent proteins of numerous colors with several highly conserved structural and physicochemical characteristics. In addition to their energy harvesting function, PBPs have shown multiple biological activities, comprising antibacterial, antioxidant, and antitumor activities. They are also applied in areas of biomedicine and bioenergy research. The present study was conducted to extract and analyze the use of phycobiliproteins as a food coating agent and microbial inhibitant to enhance the shelf life of fruits and vegetables. Phycobiliproteins were extracted from Oscillatoria sp. using the mechanochemical method and were analyzed via SDSPAGE. Purified extracts were tested for antioxidant activity, antimicrobial activity, and biopreservational effects. PBP extracts showed higher inhibition zones of 8.2 mm and 8.5 mm for E.coli and Rhizopus, respectively. The edible dip coating technique was more efficient, providing an 8-day shelf life with an 80 % freshness of fruits and vegetables. The nitric oxide scavenging activity of the PBP-3 method was 78% with a 200 ug/ml concentration. Phycobiliproteins showed antimicrobial activity against the Staphylococcus aureus and Kliebsella sp. An excellent biopreservational effect of the extract was observed from the physical appearance of the control and test group of fruit and vegetables and further from the microbial flora assay. It was concluded that the phycobiliproteins of the Oscillatoria sp. of cyanobacteria represent a potential microbial inhabitant, and their effects of biopreservation make them an effective food coating agent.

Cervical cancer is a widespread type of cancer among women worldwide, caused by an HPV virus infection. In recent years, researchers have focused on developing new targeted treatment approaches to reduce or eliminate side effects caused by standard treatment methods used in clinics. Our research aimed to investigate the p53 signalling pathways expressed in the genomic profile of HeLa and C-4 I using RNA sequencing after applying safranal. The goal is to explore the biological processes, molecular functions, and genes involved in that pathway.

To analyze the genome profile, we applied Safranal to the cervical cancer cell lines HeLa and C-4 I for 24 h. A sequencing library was created using the RNAs isolated at the end of the incubation period. After sequencing with the DNBEQ library, we analyzed p53 signaling pathways, KEGG pathways, Gene Ontology projects, cluster heat maps, and protein--protein interactions.

Based on KEGG and GO ontology, we found that safranal down-regulated the p53 signaling pathway in Hela and C-4 I cells. In total, 11 and 9 genes of HeLa and C- 4 I, respectively, are involved in this pathway. We also observed safranal-induced cell cycle arrest in the G1 phase and induced apoptosis through extrinsic and mitochondrial pathways. Furthermore, we found that safranal inhibits angiogenesis and metastasis mechanism processes. Additionally, the effect of safranal on DNA has been discovered through the activation of DNA damage repair mechanisms. Finally, we used heat map cluster analysis to demonstrate the differential expression of genes in control and safranal-treated cells, and their functions were determined using the KEGG map.

In conclusion, these data showed that the application of safranal leads to the downregulation of p53 signaling pathway, which showed its potential anti-cancer effects on cervical cancer cell lines, HeLa and C- 4 I

Lissachatina fulica is the largest invasive agricultural pest with the highest prevalence in Asian countries. At the same time, L. fulica is one of the few animal species that can regenerate organs, including the nervous system and eyes. However, its genome is poorly studied, which restricts further molecular and genetic studies of this organism. At the same time, one of the most accessible methods to study genomes is qPCR, the accuracy of the results of which depend on the selected reference genes. Therefore, the aim of this study was to predict the sequences of some genes in L. fulica using genes that are most often used as reference genes for qPCR.

In searching for homologous genes in L. fulica, actin (Act), β-tubulin (Tubb), and glyceraldehyde-3-phosphate dehydrogenase (Gapdh) were selected as commonly used reference genes in qPCR for molluscs. The corresponding amino acid sequences of their proteins were used for more accurate prediction. The amino acid sequences of ACT, TUBB, and GAPDH of the gastropod molluscs Aplysia californica, Pomacea canaliculata, and Biomphalaria glabrata as the closest related species to L. fulica were taken from the NCBI Protein database. Multiple sequence alignment was performed using Clustal Omega followed by refining the results by MUSCLE in Unipro UGENE (v. 45.0). HMM3 profiles were also constructed in Unipro UGENE and then used to search for homologous sequences in L. fulica (GigaDB repository) using HMMER (v. 3.3.2).

As a result, we found in L. fulica homologous sequences for GAPDH (Afu019240), TUBB (Afu012850), and ACT (Afu006397) and the corresponding mRNA of genes encoding these proteins. Thus, the first attempt was carried out to annotate the L. fulica genome in order to identify reference genes, which is a necessary element of any molecular and genetic study.

This research was supported by the IKBFU grant 434-К-23 “Priority 2030”.