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Background: Influenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin chains synthesized by TRIM25. However, the influenza A virus's NS1 protein hinders this process by binding to TRIM25, disrupting its association with RIG-I and preventing downstream interferon signalling, contributing to the virus's evasion of the immune response., Methods: In our study we used structural-based drug designing, molecular simulation, and binding free energy approaches to identify the potent phytocompounds from various natural product databases (>100,000 compounds) able to inhibit the binding of NS1 with the TRIM25., Results: The molecular screening identified EA-8411902 and EA-19951545 from East African Natural Products Database, NA-390261 and NA-71 from North African Natural Products Database, SA-65230 and SA- 4477104 from South African Natural Compounds Database, NEA- 361 and NEA- 4524784 from North-East African Natural Products Database, TCM-4444713 and TCM-6056 from Traditional Chinese Medicines Database as top hits. The molecular docking and binding free energies results revealed that these compounds have high affinity with the specific active site residues (Leu95, Ser99, and Tyr89) involved in the interaction with TRIM25. Additionally, analysis of structural dynamics, binding free energy, and dissociation constants demonstrates a notably stronger binding affinity of these compounds with the NS1 protein. Moreover, all selected compounds exhibit exceptional ADMET properties, including high water solubility, gastrointestinal absorption, and an absence of hepatotoxicity, while adhering to Lipinski's rule., Conclusion: Our molecular simulation findings highlight that the identified compounds demonstrate high affinity for specific active site residues involved in the NS1-TRIM25 interaction, exhibit exceptional ADMET properties, and adhere to drug-likeness criteria, thus presenting promising candidates for further development as antiviral agents against influenza A virus infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be - 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was - 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was - 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be - 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sayaf, Ullah Khalid, Hameed, Alshammari, Khan, Mohammad, Alghamdi, Wei and Yeoh.)

Based on constructivism theory and the Information System Success Model, this study suggests a research model that examines the factors that influence students' collaborative engagement and satisfaction in an e-learning system setting. This study intends to validate the theoretical concepts and the Information System Success Model (ISSM) on e-learning platforms for user satisfaction and collaborative activity in order to expand the adoption of e-learning systems in higher education. This research used a questionnaire as the primary data collection method to obtain information for the study from 300 responses from different students at the University of Bisha, who all use e-learning platforms. The results were achieved using structural equation modeling, a quantitative research technique (SEM-AMOS). All of the study's hypotheses were supported, according to the findings of the structural model and hypothesis testing. The outcomes of peer interaction (IP) and instructor interaction (IL) have a favorable impact on satisfaction and teamwork, which have a beneficial impact on the usage of e-learning in higher education. This is advantageous for sustainability as well as the adoption of e-learning systems. Finally, the study demonstrates that user happiness and collaborative involvement have a favorable impact on the utilization of e-learning systems. As a result, universities should promote e-learning as a long-term educational strategy., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author.)

The COVID-19 pandemic has rekindled interest in online learning as a desirable substitute. In Saudi Arabia's educational system, technology and online learning are becoming more and more significant. In order to prepare students for the digital age and Saudi Vision 2030, there is an increasing desire for educational institutions to use e-learning. Students and faculty at Saudi institutions now have more opportunities to better grasp the globalized digital age thanks to the integration and acceptance of digital technology into learning and teaching. Therefore, this study aims to analyze and investigate the educational quality, social influence, and TAM Model factors that increase the students' attitude toward using e-learning; thus, it affects students' satisfaction and academic performance. The study was conducted at two universities in Saudi Arabia. Structural equation modeling (SEM) and route analysis were used to evaluate the research model and analyze data from e-learning users through a questionnaire. The findings revealed that perceived ease of use (PEU) and perceived usefulness (PU) mediate the effects of educational quality (EDQ), social influence (SOI), and perceived enjoyment (PE), which in turn affect students' attitude toward use (ATU), and students' satisfaction with using e-learning systems (SSE). Additionally, the results demonstrated that the mediator factors had favorable "R square (R 2 )" values for adopting e-learning systems in higher education, with PEU = 0.562, PU = 0.712, ATU = 0.608, and SSE = 0.636. The hypotheses' findings led to the development of a validated instrument to measure students' online learning in Saudi Arabia's higher education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alqahtani, Alamri, Sayaf and Al-Rahmi.)

Previous research on e-learning in underdeveloped countries has seldom taken a comprehensive approach. A literature review of recent published research in the field of e-learning use during the COVID-19 epidemic is also included in this study. Therefore, the aim of this study is to look at the technology acceptance model (TAM) and information systems (IS) performance models to see how system quality (SYQ), service quality (SEQ), and quality of life (QoL) are related, as well as the mediating impact of perceived ease of use (PEU) and perceived usefulness (PU), affect students' behavioral intention to use (BIU), and actual use of an e-learning system (AUE) as sustainability for education during the COVID-19 pandemic. Path analysis and structural equation modeling (SEM) were used to evaluate the research model, using the data from e-learning users obtained through a survey. Participants were e-learning users from two Saudi Arabian public universities. The findings revealed that PU and ease of use were positively correlated and influenced by SYQ, SEQ, and QoL in education, and that PEU and PU were positively influenced by students' BIU and AUE system. In the sense of e-learning in developing countries, previous studies rarely looked at an integrated model. This paper also attempts to provide a recently published study in the area of the use of an e-learning system as sustainability for education during the COVID-19 pandemic. There is a lot of ongoing research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alqahtani, Alamri, Sayaf and Al-Rahmi.)

A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study uses computational drug screening and molecular dynamics simulation approaches (replicated) to identify novel drugs that can inhibit the binding of the receptor-binding domain (RBD) with hACE2. Screening of the North African, East African and North-East African medicinal compound databases by employing a multi-step screening approach revealed four compounds, namely (-)-pipoxide (C1), 2-( p -hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[( E )-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), with excellent anti-viral properties against the RBD of the omicron variant. Investigation of the dynamics demonstrates stable behavior, good residue flexibility profiles, and structural compactness. Validation of the top hits using computational bioactivity analysis, binding free energy calculations and dissociation constant ( K D ) analysis also indicated the anti-viral properties of these compounds. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging omicron variant of SARS-CoV-2., Competing Interests: There are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Snow trout (Schizothorax plagiostomus) is an economically important freshwater fish, mostly found in northern areas of water reservoirs of Pakistan. The current study was conducted in River Swat to analyze the bioaccumulation of heavy metals (Pb, Cr, Ni, and Zn) in tissues of Schizothorax plagiostomus. Tissues were extracted and dissolved in perchloric acid (HClO4) and nitric acid (HNO3) along with hotplate. The heavy metals, zinc (Zn), lead (Pb), chromium (Cr), and Nickel (Ni) were determined using Perkin Elmer 2380 atomic absorption spectrophotometer. Results shows great variation in the content of the metal related to tissue type and sampling sites. A high concentration of bioaccumulation was reported at Charbagh, whereas lowest at Odigram: Charbagh>Landakai>Odigram. In the same way, Cr was the most accumulated heavy metal followed by lead, nickel, and Zinc.

Breast cancer is the most common cause of death in women worldwide. Approximately 5%-10% of instances are attributed to mutations acquired from the parents. Therefore, it is highly recommended to design more potential drugs and drug targets to eradicate such complex diseases. Network-based gene expression profiling is a suggested tool for discovering drug targets by incorporating various factors such as disease states, intensities based on gene expression as well as protein-protein interactions. To find prospective biomarkers in breast cancer, we first identified differentially expressed genes (DEGs) statistical methods p-value and false discovery rate were initially used. Of the total 82 DEGs, 67 were upregulated while the remaining 17 were downregulated. Sub-modules and hub genes include VEGFA with the highest degree, followed by 15 CCND1 and CXCL8 with 12-degree score was found. The survival analysis revealed that all the hub genes have important role in the development and progression of breast cancer. Enrichment analysis revealed that most of these genes are involved in signaling pathways and in the extracellular spaces. We also identified transcription factors and kinases, which regulate proteins in the DEGs PPI. Finally, drugs for each hub genes were identified. These results further expanded the knowledge regarding important biomarkers in breast cancer.

Helicobacter Pylori is a known causal agent of gastric malignancies and peptic ulcers. The extremophile nature of this bacterium is protecting it from designing a potent drug against it. Therefore, the use of computational approaches to design antigenic, stable and safe vaccine against this pathogen could help to control the infections associated with it. Therefore, in this study, we used multiple immunoinformatics approaches along with other computational approaches to design a multi-epitopes subunit vaccine against H. Pylori. A total of 7 CTL and 12 HTL antigenic epitopes based on c-terminal cleavage and MHC binding scores were predicted from the four selected proteins (CagA, OipA, GroEL and cagA). The predicted epitopes were joined by AYY and GPGPG linkers. Β-defensins adjuvant was added to the N-terminus of the vaccine. For validation, immunogenicity, allergenicity and physiochemical analysis were conducted. The designed vaccine is likely antigenic in nature and produced robust and substantial interactions with Toll-like receptors (TLR-2, 4, 5, and 9). The vaccine developed was also subjected to an in silico cloning and immune response prediction model, which verified its efficiency of expression and the immune system provoking response. These analyses indicate that the suggested vaccine may produce particular immune responses against H. pylori, but laboratory validation is needed to verify the safety and immunogenicity status of the suggested vaccine design.