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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, affecting millions of people and challenging the public health framework globally. While the definitive cause of AD remains unclear, researchers are concentrating their efforts on several prominent theories. Currently, there are very few FDA-approved medications for AD, and these primarily alleviate symptoms rather than alter the disease’s progression. In response, research efforts focus on developing new medicines that address the complex nature of AD through multi-targeted approaches. Multitarget-directed ligands (MTDLs) are a promising treatment strategy for AD, despite the significant challenges they pose. This review examines recent advancements in designing prospective targeted MTDLs to combat AD, with a focus on categorizing the lead generation process and investigating the integration methods of key pharmacophores within the 2024–2025 timeframe. The review highlights numerous examples of novel MTDLs that address various AD hallmarks, demonstrating their broad therapeutic potential. These targets and activities include cholinesterase (AChE and/or BuChE) inhibition, monoamine oxidase (MAO-A and/or MAO-B) inhibition, antioxidant activity, amyloid-beta (Aβ) aggregation inhibition, tau protein aggregation inhibition, glycogen synthase kinase 3β (GSK-3β) inhibition, calcium channel blockade, anti-inflammatory activity, and other hallmarks.

Marburg virus (MARV), a highly pathogenic member of the Filoviridae family, causes severe hemorrhagic fever with a high case fatality rate and currently lacks effective therapeutics. The viral entry process, mediated by the interaction between the MARV glycoprotein (GP) and host receptor C-type lectin domain family 4 member M (CLEC4M) (L-SIGN), represents a critical target for early-stage intervention. The active compounds from BindingDB and the decoy from DUDE were used. The RDKit was used for feature engineering. Machine learning models were trained on an initial dataset consisting of 56 active chemicals and 1232 decoys. Among the tested algorithms, the Random Forest model demonstrated superior performance, achieving the highest discriminative ability (AUC = 0.93, MCC = 0.88) on the test set. Virtual screening of 11,032 phytochemicals resulted in 120 predicted actives, of which 42 compounds satisfied drug-likeness criteria. Subsequent molecular docking identified three lead compounds (PubChem IDs: 42608095, 5281601, and 11243993) with moderate-to-promising binding affinities (-6.3 to -6.5 kcal/mol) toward the CLEC4M binding site. ADMET analysis revealed favorable pharmacokinetic and toxicity profiles for the selected lead compounds. DFT calculations of the three compounds highlighted their electronic stability and reactive nature, indicating that PubChem IDs 42608095 and 5281601 possess particularly stable electronic properties conducive to favorable target interactions. Combining machine learning models with molecular docking and Molecular Dynamics (MD) simulations worked well in finding promising phytochemical inhibitors. The MM/GBSA binding free energy calculations further confirmed binding affinities, with values of -10.83 and -11.08 kcal/mol, respectively, suggesting favorable complex stability. These findings provide a pathway for developing new antiviral agents against MARV, pending further experimental validation and optimization.

In the race to combat ever-evolving diseases, the drug discovery process often faces the hurdles of high-cost and time-consuming procedures. To tackle these challenges and enhance the efficiency of identifying new therapeutic agents, we introduce VirtuDockDL, which is a streamlined Python-based web platform utilizing deep learning for drug discovery. This pipeline employs a Graph Neural Network to analyze and predict the effectiveness of various compounds as potential drug candidates. During the validation phase, VirtuDockDL was instrumental in identifying non-covalent inhibitors against the VP35 protein of the Marburg virus, a critical target given the virus’s high fatality rate and limited treatment options. Further, in benchmarking, VirtuDockDL achieved 99% accuracy, an F1 score of 0.992, and an AUC of 0.99 on the HER2 dataset, surpassing DeepChem (89% accuracy) and AutoDock Vina (82% accuracy). Compared to RosettaVS, MzDOCK, and PyRMD, VirtuDockDL outperformed them by combining both ligand- and structure-based screening with deep learning. While RosettaVS excels in accurate docking but lacks high-throughput screening, and PyRMD focuses on ligand-based methods without AI integration, VirtuDockDL offers superior predictive accuracy and full automation for large-scale datasets, making it ideal for comprehensive drug discovery workflows. These results underscore the tool’s capability to identify high-affinity inhibitors accurately across various targets, including the HER2 protein for cancer therapy, TEM-1 beta-lactamase for bacterial infections, and the CYP51 enzyme for fungal infections like Candidiasis. To sum up, VirtuDockDL combines user-friendly interface design with powerful computational capabilities to facilitate rapid, cost-effective drug discovery and development. The integration of AI in drug discovery could potentially transform the landscape of pharmaceutical research, providing faster responses to global health challenges. The VirtuDockDL is available at https://github.com/FatimaNoor74/VirtuDockDL .

While chemotherapy is the most effective therapeutic approach for treating a variety of cancer patients, commonly used chemotherapeutic agents, often induce several adverse effects. Escalating evidence indicates that chemotherapeutics, particularly doxorubicin (DOX) and cyclophosphamide (CPS), induce cognitive impairment associated with central nervous system toxicity. This study was performed to determine neuroprotective effects of Oroxylum indicum extract (OIE) in regard to preventing chemotherapy induced cognitive impairment (CICI) occurring after 4 cycles of DOX (2mg/kg) and CPS (50mg/kg) combination chemotherapy in male C57BL/6J mice. OIE significantly prevented the chemotherapy impaired short-term cognitive performance, exploratory behavior associated with cognitive performance, cognitive performance, and spatial learning and memory in the Y-maze, Open-Field, Novel Object Recognition, and Morris Water Maze tests, respectively. These data suggest that OIE protects from the CICI. OIE decreased the reactive oxygen species and lipid peroxide generated by the chemotherapy treatment in the brain, while also blocking the chemotherapy-induced glutathione depletion. These results establish that OIE exhibits potent antioxidant activity in chemotherapy treated mice. Notably, OIE significantly increased the Complex-I and Complex-IV activities in the brain, indicating that OIE enhances mitochondrial function in the brain. In silico analysis of the major active chemical constituents (Oroxylin A, Baicalein and Chrysin) of OIE indicated that OIE has a favorable absorption, distribution, metabolism and excretion (ADME) profile. Taken together, our results are consistent with the conclusion that OIE prevents CICI by counteracting oxidative stress and perhaps by improving mitochondrial function.

This study aims to assess the general population's awareness, attitude, and adherence regarding COVID-19 and quarantine in Saudi Arabia. A descriptive cross-sectional design with a consecutive sampling method was used in this study. All accessible Saudi population during the study period were invited to participate in the survey from 1st April to 25th April 2020. The study questionnaire was constructed by the researchers based on experts' consultation. A total sample of 1998 respondents with complete data was included in the survey. A total of 1936 participants reported that they were aware of regarding COVID-19 outbreak (96.9%). The most identified symptom was fever (92.3%; 1843), followed by respiratory distress (90.8%; 1813). About 81% of the participants reported that quarantine should be applied with travel or contact with infected persons. Also, 98.3% of the participants reported that the quarantine period should be a minimum of 14 days. In total, more than three-quarters of the participants had good awareness levels regarding COVID-19 and quarantine. This study showed that the Saudi population had very high levels of awareness, adherence regarding COVID-19 quarantine and isolation measures.

Background: Breast cancer, the most prevalent cancer among women globally, develops primarily in the breast’s ducts or lobules. Drug resistance is a significant challenge in treating advanced cases, contributing to over 685,000 breast cancer-related deaths annually, and identifying novel compounds that inhibit key proteins is crucial for developing effective therapies. Methods: In this study, five transferase proteins with PDB IDs were selected due to their involvement in breast cancer: 1A52, 3PP0, 4EJN, 4I23, and 7R9V. Multitargeted docking studies were conducted using three different docking strategies and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) to calculate the binding affinities against the ZINC Natural compound library. Isoetin (ZINC000006523948), found mainly in Isoetaceae, was identified, and the results were compared with the Food and Drug Administration (FDA)-approved drug Tucatinib. In addition, molecular interaction fingerprints and pharmacokinetic profiling were evaluated. We also performed 5 ns WaterMap simulations to identify hydration sites and interactions, followed by 100 ns molecular dynamics (MD) simulations and MM/GBSA to assess the stability of the Isoetin–protein complexes. Results: The docking results indicated that Isoetin demonstrated superior binding and docking scores ranging from −9.901 to −13.903 kcal/mol compared to Tucatinib, which showed values between −4.875 and −10.948 kcal/mol, suggesting Isoetin’s potential efficacy as a therapeutic agent for breast cancer. Interaction fingerprints revealed significant interactions between Isoetin and key residues, including 28LEU, 12MET, 9PHE, 7ASP, 6ASN, and 6THR. The pharmacokinetics and DFT analysis of Isoetin supported its potential as a viable drug candidate. Furthermore, the 5 ns WaterMap simulations identified various hydration sites, and the 100 ns MD simulations showed that the Isoetin–protein complexes exhibited minimal deviations and fluctuations, indicating better stability than Tucatinib, and MM/GBSA confirmed Isoetin’s superior binding stability. Conclusions: Isoetin, a natural compound identified through in silico screening, demonstrates significant promise as a potential therapeutic agent for breast cancer as it outperforms the FDA-approved drug Tucatinib, the respective native and FDA-approved drug. However, experimental validation is necessary before considering Isoetin for clinical use.

Background Morganellaceae (including Proteus , Providencia , and Morganella ) are opportunistic pathogens increasingly associated with antimicrobial resistance (AMR). Long-term trend data, particularly from the Middle East, remain scarce. This study aimed to characterize the epidemiology, demographic and clinical characteristics, and antimicrobial resistance dynamics of Morganellaceae isolates in southern Saudi Arabia over a 12-year period, with a specific focus on carbapenem resistance (CRE), multidrug resistance (MDR), and difficult-to-treat resistance (DTR), as well as their genus-level variability and unique resistance phenotypes. Methods A 12-year retrospective cross-sectional study (2012–2024) was conducted at Aseer Central Hospital, southern Saudi Arabia. Non-duplicate clinical isolates from patients ≥ 12 years were identified using VITEK ® 2, with susceptibility interpreted according to CLSI guidelines. CRE, MDR, and DTR were defined by standardized criteria. Logistic regression was applied to model annual non-susceptibility trends, reported as odds ratios (ORs) and annual percent change (APC). Subgroup analyses explored genus-level differences, ICU versus non-ICU settings, and intra-genus variability. Results A total of 3,338 isolates were recovered, predominantly Proteus spp. (72.4%), followed by Providencia (18.6%) and Morganella (9.0%). Overall prevalence of CRE, MDR, and DTR was 25.7%, 44.8%, and 13.2%, respectively. Providencia showed the highest resistance burdens (CRE 33.6%, MDR 68.1%, DTR 23.2%), significantly exceeding Proteus (CRE 23.3%, MDR 39.1%, DTR 10.0%) and Morganella (CRE 29.3%, MDR 42.3%, DTR 9.2%) (all p  < 0.001). Within CRE, 32.8% of isolates were non-susceptible to imipenem yet remained susceptible to meropenem and ertapenem. Compared with non-ICU isolates, ICU isolates exhibited higher MDR (49.6% vs. 41.5%, p  < 0.001) but lower CRE (23.1% vs. 27.5%, p  = 0.006), while DTR prevalence was comparable. Temporal analysis demonstrated significant declines in resistance to cephalosporins, fluoroquinolones, aminoglycosides, and Trimethoprim–Sulfamethoxazole, whereas imipenem resistance rose sharply (APC + 48.6%; OR 1.49, 95% CI 1.43–1.54, p  < 0.001); meropenem and ertapenem remained stable. Conclusions Morganellaceae infections in southern Saudi Arabia carry substantial MDR and CRE burdens with pronounced genus-level variability,with Providencia posing the greatest therapeutic challenge. While several antibiotic classes showed declining resistance, the sharp rise in imipenem non-susceptibility is concerning. Strengthening species-level AST reporting and integrating Morganellaceae resistance data into healthcare-associated infection (HAI) surveillance frameworks are essential, particularly in ICU settings where outbreak risk is greatest.

Objective. The study aims to determine the prevalence of multidrug-resistant A. baumannii in Aseer Region, Kingdom of Saudi Arabia. Methods. This study evaluated the antibiotic susceptibility of ninety-four (n = 94) clinical isolates of A. baumannii. The isolates were collected from the south region of Saudi Arabia, and notably Aseer Region, during the period from 15 October 2014 to 15 January 2015. The isolates were tentatively identified as A. baumannii by routine bench tests and were confirmed by using VITEK® 2 Compact. The latest instrument was used to identify antibiotic susceptibility of these isolates. Results. Antibiotic susceptibility in this study showed that 69% of these isolates were multidrug-resistant strains. Moreover, they were highly resistant to carbapenem drugs. Several strains of these isolates were found to be extremely resistant to test antibiotics and were only sensitive to one or two of them. Conclusion. High rate of multidrug-resistant A. baumannii bacteraemia has emerged in the south region of Saudi Arabia as an important health problem. Therefore, it is considered as a new threat in hospitals, which requires a tremendous effort to stop its escalation and spread.

Chronic inflammation is a key culprit factor in the onset and progression of several diseases. Novel and pharmacologically effective therapeutic approaches are needed for new treatment remedy or improved pharmacokinetics and pharmacodynamics for existing synthetic drugs, in particular natural products. Boswellic acids are well-known natural products, with capacity to effectively retard inflammation without severe adverse effects. However, the therapeutic use of Boswellic acids are greatly hindered by its poor pharmacokinetic properties. Co-administration strategies that facilitate the oral absorption and distribution of Boswellic acids should lead to a safe and more effective use of this product prophylactically and therapeutically in inflammatory disorders. In this study, we examined the effect of Piper longum extract on the absorption and bioavailability of Boswellic acid in rabbits. In addition, we further explored computational pharmacodynamic interactions between Piper longum and Boswellic acid. Piper longum extract at 2.5 and 10 mg/kg, increased the bioavailability of Boswellic acid ( p < 0.05). Based on our drug-based computational modeling, cytochrome P450 (CYP450)-mediated mechanism was involved in increased bioavailability. These findings confirmed that Piper longum with Boswellic acid may be administered orally together for effective therapeutic efficacy. Thus, our studies support the application of Piper longum with Boswellic acid as a novel therapeutic avenue in diseases associated with inflammation.

ObjectiveTo assess the efficacy and safety of the induction chemotherapy's combination of docetaxel, cisplatin, and 5-fluorouracil (TPF) in Oral Squamous Cell Carcinoma (OSCC) patients and its positive outcomes on tumor size and surgical resection.MethodA retrospective chart review of patient's medical records was conducted from 2018 to 2023. All patients diagnosed with OSCC and who received induction chemotherapy combination of TPF were included in the study. Patients with other conditions that affect chemotherapy tolerability, other primary malignancy, or incomplete medical records were excluded. Descriptive analysis was undertaken to summarize the data pertaining to tumors before and after administration of the TPF chemotherapy.ResultFive patients met the inclusion criteria. All five patients experienced a reduction in tumor size after receiving the TPF induction chemotherapy. Three patients showed a downstaging to [stage 0] after surgical resection. Specifically, one patient demonstrated a reduction in overall stage from [IVb] to [IVa] after receiving TPF induction chemotherapy, and two patients demonstrated a noteworthy improvement in N staging, reducing from [N2c] to [N2b]. In contrast, the fourth patient slightly improved after the induction chemotherapy and surgical resection procedures. However, the stage of the fifth patient remained unchanged before and after the treatment approach.ConclusionThe study shows that implementing TPF induction chemotherapy to surgical resection improves clinical outcomes in a subset of patients with advanced OSCC without any harmful consequences.