Displaying publications 181 - 200 of 450 in total

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  1. Devi NM, Nagarajan S, Singh CB, Khan MMA, Khan A, Khan N, et al.
    Chem Biodivers, 2023 Sep 16.
    PMID: 37715949 DOI: 10.1002/cbdv.202300970
    BACKGROUND: Alpinia calcarata (AC) Roscoe of Zingiberaceae popularly known as lesser galangal has a widespread occurrence in China, India, Sri-Lanka, Bangladesh, Malaysia, Indonesia and Thailand. Essential oil (Eoil) was obtained from leaves/rhizomes of AC via hydro-distillation process.

    METHODS: To identify chemical ingredients in oil from leaves/rhizomes of AC through GC/MS technique for volatile components and their anti-oxidant, inflammatory/diabetic activities.

    RESULTS: The 38 and 65 components were found to make up 99.9 and 99.6 %, respectively in total of Eoil composition of AC leaves/rhizomes. Key chemical constituents were eucalyptol (28.7 % in leaves; 25.4 % in rhizomes), camphor (12.8 % in leaves; 4.2 % in rhizomes), and carotol (9.8 % in leaves; 5.6 % in rhizomes) found in oil of AC leaves/rhizomes. Colorimetric assay showed anti-oxidant activities in leaves and rhizomes are IC50 =71.01±0.71 μg/mL and IC50 =73.83±0.49 μg/mL, respectively in the Eoils. Eoils had high anti-oxidant capabilities in IC50 -values of AC-L-Eoil=43.09±0.82&AC-Rh-Eoil=68.11±0.87 in reducing power in μg/mL was found. Albumin test of rhizome oil had IC50 -values of 15.19±0.25 μg/mL. Concentrations range of 7.81 μg/mL and 250 μg/mL in the Eoils of AC leaves and rhizome, respectively by α-glucosidase inhibition assay.

    CONCLUSION: Our findings demonstrated that leaf oil was slightly more promising results than rhizome oil of AC extract, which was ultimately showed medicinal potential of secondary metabolites with anti-oxidant, diabetic/inflammatory activities. Further, Eoils of AC have a wide range of pharmacological potential and promising anti-diabetic effects.

  2. Akbar N, Javed M, Arif Khan A, Masood A, Ahmed N, Mehmood RY, et al.
    ACS Omega, 2023 Aug 22;8(33):30095-30108.
    PMID: 37636959 DOI: 10.1021/acsomega.3c02457
    The degradation of organic dye pollutants is a critical environmental issue that has garnered significant attention in recent years. To address this problem, we investigated the potential of CaCrO4 chromite (CCO) as a photocatalyst for the degradation of cationic and anionic dye solutions under sunlight irradiation. CaCrO4 was synthesized via a sol-gel auto-combustion route and sintered at 900 °C. The Rietveld refined XRD profile confirmed the zircon-type structure of CaCrO4 crystallized in the tetragonal unit cell with I41/amd space group symmetry. The surface morphology of the sample was investigated by field emission scanning electron microscopy (FESEM), which revealed the polyhedral texture of the grains. Energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) studies were carried out to analyze the elemental composition and chemical states of the ions present in the compound. Fourier transform infrared (FT-IR) spectroscopy analysis revealed the vibrational modes corresponding to the tetrahedral and dodecahedral metal oxide bonds. The optical band gap was approximated to be in the range of 1.928 eV by using the Tauc relation. The CaCrO4 catalyst with different contents (5, 20, 35, and 50 mg) was investigated for its photocatalytic performance for the degradation of RhB dye solution under sunlight irradiation using a UV-Vis spectrometer over the experimental wavelength range of 450-600 nm. The degradation efficacy increased from 70.630 to 93.550% for 5-35 mg and then decreased to 68.720% for 50 mg in 140 min under visible light illumination. The comparative study demonstrates that a higher degradation rate was achieved for cationic than anionic dyes in the order RhB > MB > MO. The highest deterioration (93.80%) was achieved for the RhB dye in 140 min. Equilibrium and kinetic studies showed that the adsorption process followed the Langmuir isotherm and pseudo-second-order models, respectively. The maximum adsorption capacity of 21.125 mg/g was observed for the catalyst concentration of 35 mg. From the cyclic test, it has been observed that the synthesized photocatalyst is structurally and morphologically stable and reusable. The radical trapping experiment demonstrated that superoxide and hydroxyl radicals were the primary species engaged in the photodegradation process. A possible mechanism for the degradation of RhB has been proposed. Hence, we conclude that CaCrO4 can be used as an efficient photocatalyst for the remediation of organic dye pollutants from the environment.
  3. Sayaf AM, Ahmad H, Aslam MA, Ghani SA, Bano S, Yousafi Q, et al.
    Appl Biochem Biotechnol, 2023 Nov;195(11):6959-6978.
    PMID: 36961512 DOI: 10.1007/s12010-023-04466-1
    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.
  4. Backhaus I, Fitri M, Esfahani M, Ngo HT, Lin LJ, Yamanaka A, et al.
    Asia Pac J Public Health, 2023 May;35(4):244-250.
    PMID: 37226778 DOI: 10.1177/10105395231172311
    In this study, we aimed to investigate the prevalence of poor mental health and its association with loneliness and social support among 3531 undergraduate students in nine Asian countries. Mental health was assessed using the Self-Reporting Questionnaire, which was developed by the World Health Organization. Across the entire sample, we detected that nearly half of the students reported poor mental health according to the Self-Reporting Questionnaire and nearly one out of seven students felt lonely. While feeling lonely increased the odds of experiencing poor mental health (odds ratio [OR]), moderate (OR: 0.35) and strong social support (OR: 0.18) decreases the odds of experiencing poor mental health. The high prevalence of poor mental health calls for further in-depth investigations and implementation of mental health support interventions.
  5. Imran M, Ahmed S, Abdullah AZ, Hakami J, Chaudhary AA, Rudayni HA, et al.
    Luminescence, 2023 Jul;38(7):1064-1086.
    PMID: 36378274 DOI: 10.1002/bio.4408
    The penicillin derivative amoxicillin (AMX) plays an important role in treating various types of infections caused by bacteria. However, excessive use of AMX may have negative health effects. Therefore, it is of utmost importance to detect and quantify the AMX in pharmaceutical drugs, biological fluids, and environmental samples with high sensitivity. Therefore, this review article provides valuable and up-to-date information on nanostructured material-based optical and electrochemical sensors to detect AMX in various biological and chemical samples. The role of using different nanostructured materials on the performance of important optical sensors such as colorimetric sensors, fluorescence sensors, surface-enhanced Raman scattering sensors, chemiluminescence/electroluminescence sensors, optical immunosensors, optical fibre-based sensors, and several important electrochemical sensors based on different electrode types have been discussed. Moreover, nanocomposites, polymer, and MXenes-based electrochemical sensors have also been discussed, in which such materials are being used to further enhance the sensitivity of these sensors. Furthermore, nanocomposite-based photo-electrochemical sensors and the market availability of biosensors including AMX have also been discussed briefly. Finally, the conclusion, challenges, and future perspectives of the above-mentioned sensing techniques for AMX detection are presented.
  6. Khan A, Vallini L, Aziz S, Khan H, Zaib K, Nigar K, et al.
    Eur J Hum Genet, 2022 Jun;30(6):740-746.
    PMID: 35217804 DOI: 10.1038/s41431-022-01057-2
    Northern Pakistan is home to many diverse ethnicities and languages. The region acted as a prime corridor for ancient invasions and population migrations between Western Eurasia and South Asia. Kho, one of the major ethnic groups living in this region, resides in the remote and isolated mountainous region in the Chitral Valley of the Hindu Kush Mountain range. They are culturally and linguistically distinct from the rest of the Pakistani population groups and their genetic ancestry is still unknown. In this study, we generated genome-wide genotype data of ~1 M loci (Illumina WeGene array) for 116 unrelated Kho individuals and carried out comprehensive analyses in the context of worldwide extant and ancient anatomically modern human populations across Eurasia. The results inferred that the Kho can trace a large proportion of their ancestry to the population who migrated south from the Southern Siberian steppes during the second millennium BCE ~110 generations ago. An additional wave of gene flow from a population carrying East Asian ancestry was also identified in the Kho that occurred ~60 generations ago and may possibly be linked to the expansion of the Tibetan Empire during 7th to 9th centuries CE (current era) in the northwestern regions of the Indian sub-continent. We identified several candidate regions suggestive of positive selection in the Kho, that included genes mainly involved in pigmentation, immune responses, muscular development, DNA repair, and tumor suppression.
  7. Yaseen M, Rawat SK, Khan U, Sarris IE, Khan H, Negi AS, et al.
    Nanotechnology, 2023 Sep 14;34(48).
    PMID: 37625394 DOI: 10.1088/1361-6528/acf3f6
    The customization of hybrid nanofluids to achieve a particular and controlled growth rate of thermal transport is done to meet the needs of applications in heating and cooling systems, aerospace and automotive industries, etc. Due to the extensive applications, the aim of the current paper is to derive a numerical solution to a wall jet flow problem through a stretching surface. To study the flow problem, authors have considered a non-Newtonian Eyring-Powell hybrid nanofluid with water and CoFe2O4and TiO2nanoparticles. Furthermore, the impact of a magnetic field and irregular heat sink/source are studied. To comply with the applications of the wall jet flow, the authors have presented the numerical solution for two cases; with and without a magnetic field. The numerical solution is derived with a similarity transformation and MATLAB-based bvp4c solver. The value of skin friction for wall jet flow at the surface decreases by more than 50% when the magnetic fieldMA=0.2is present. The stream function value is higher for the wall jet flow without the magnetic field. The temperature of the flow rises with the dominant strength of the heat source parameters. The results of this investigation will be beneficial to various applications that utilize the applications of a wall jet, such as in car defrosters, spray paint drying for vehicles or houses, cooling structures for the CPU of high-processor laptops, sluice gate flows, and cooling jets over turbo-machinery components, etc.
  8. Sayaf AM, Ullah Khalid S, Hameed JA, Alshammari A, Khan A, Mohammad A, et al.
    Front Pharmacol, 2023;14:1202128.
    PMID: 37670941 DOI: 10.3389/fphar.2023.1202128
    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.
  9. Mallhi TH, Salman M, Khan YH, Khan FU, Butt MH, Ung COL, et al.
    Front Pediatr, 2023;11:1298691.
    PMID: 38078334 DOI: 10.3389/fped.2023.1298691
  10. Suleman M, Ahmad T, Shah K, Albekairi NA, Alshammari A, Khan A, et al.
    Front Pharmacol, 2023;14:1328308.
    PMID: 38269277 DOI: 10.3389/fphar.2023.1328308
    Amid the ongoing monkeypox outbreak, there is an urgent need for the rapid development of effective therapeutic interventions capable of countering the immune evasion mechanisms employed by the monkeypox virus (MPXV). The evasion strategy involves the binding of the F3L protein to dsRNA, resulting in diminished interferon (IFN) production. Consequently, our current research focuses on utilizing virtual drug screening techniques to target the RNA binding domain of the F3L protein. Out of the 954 compounds within the South African natural compound database, only four demonstrated notable docking scores: -6.55, -6.47, -6.37, and -6.35 kcal/mol. The dissociation constant (KD) analysis revealed a stronger binding affinity of the top hits 1-4 (-5.34, -5.32, -5.29, and -5.36 kcal/mol) with the F3L in the MPXV. All-atom simulations of the top-ranked hits 1 to 4 consistently exhibited stable dynamics, suggesting their potential to interact effectively with interface residues. This was further substantiated through analyses of parameters such as radius of gyration (Rg), Root Mean Square Fluctuation, and hydrogen bonding. Cumulative assessments of binding free energy confirmed the top-performing candidates among all the compounds, with values of -35.90, -52.74, -28.17, and -32.11 kcal/mol for top hits 1-4, respectively. These results indicate that compounds top hit 1-4 could hold significant promise for advancing innovative drug therapies, suggesting their suitability for both in vivo and in vitro experiments.
  11. Kaleem S, Ahmad T, Wahid A, Khan HH, Mallhi TH, Al-Worafi YM, et al.
    PLoS One, 2024;19(2):e0288834.
    PMID: 38300948 DOI: 10.1371/journal.pone.0288834
    The study aims to assess the health-related Quality of Life (HRQOL) and its association with socio-demographic factors among the Afghan refugees residing in Quetta, Pakistan. For this purpose, a cross-sectional, descriptive study design by adopting Euro QOL five dimensions questionnaire (EQ-5D) for the assessment of HRQOL was conducted by approaching Afghan refugees from the camp and other areas of Quetta, Pakistan. Furthermore, this study also involved descriptive analysis to expound participant's demographic characteristics while inferential statistics (Kruskal-Wallis and Mann-Whitney test, P < 0.05) were used to compare EQ-5D scale scores. All analyses were performed using SPSS v 20. Herein, a total of 729 participants were enrolled and were subsequently (n = 246, 33.7%) categorized based on their age of 22-31 years (31.30 ± 15.40). The results of mean EQ-5D descriptive score (0.85 ± 0.20) and EQ-VAS score (78.60 ± 11.10) indicated better HRQOL in the current study respondents as compared to studies conducted in other refugee camps around the globe. In addition, demographic characteristics including age, marital status, locality, years of living as refugees, life as a refugee residing out of Pakistan, place of residence in Afghanistan, educational qualification, occupation, and arrested for crime were the statistically significant predictors (P < 0.05) of EQ-5D index scores. However, gender, living status, monthly income, preferred place of treatment were non-significant predictors (P > 0.05). The results of current study provided evidence for a model that correlated with participant's socio-demographic information and HRQOL. Moreover, this study also revealed a baseline assessment for the health status of Afghan refugees, interestingly, these results could be applied for improving HRQOL of the given participants. In conclusion, the HRQOL of Afghan refugees residing in Quetta, Pakistan can largely be improved by providing adequate healthcare facilities, education and employment opportunities, mental and social support, and providing adequate housing and basic necessities of life.
  12. Rubnawaz S, Kayani WK, Akhtar N, Mahmood R, Khan A, Okla MK, et al.
    Molecules, 2021 Aug 11;26(16).
    PMID: 34443462 DOI: 10.3390/molecules26164874
    Ajuga bracteosa Wall. ex Benth. is an endangered medicinal herb traditionally used against different ailments. The present study aimed to create new insight into the fundamental mechanisms of genetic transformation and the biological activities of this plant. We transformed the A. bracteosa plant with rol genes of Agrobacterium rhizogenes and raised the regenerants from the hairy roots. These transgenic regenerants were screened for in vitro antioxidant activities, a range of in vivo assays, elemental analysis, polyphenol content, and different phytochemicals found through HPLC. Among 18 polyphenolic standards, kaempferol was most abundant in all transgenic lines. Furthermore, transgenic line 3 (ABRL3) showed maximum phenolics and flavonoids content among all tested plant extracts. ABRL3 also demonstrated the highest total antioxidant capacity (8.16 ± 1 μg AAE/mg), total reducing power, (6.60 ± 1.17 μg AAE/mg), DPPH activity (IC50 = 59.5 ± 0.8 μg/mL), hydroxyl ion scavenging (IC50 = 122.5 ± 0.90 μg/mL), and iron-chelating power (IC50 = 154.8 ± 2 μg/mL). Moreover, transformed plant extracts produced significant analgesic, anti-inflammatory, anticoagulant, and antidepressant activities in BALB/c mice models. In conclusion, transgenic regenerants of A. bracteosa pose better antioxidant and pharmacological properties under the effect of rol genes as compared to wild-type plants.
  13. Suleman M, Khan TA, Ejaz H, Maroof S, Alshammari A, Albekairi NA, et al.
    Microb Pathog, 2024 Apr;189:106572.
    PMID: 38354987 DOI: 10.1016/j.micpath.2024.106572
    The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.
  14. Ali I, Wei DQ, Khan A, Feng Y, Waseem M, Hussain Z, et al.
    Biotechnol Appl Biochem, 2024 Apr;71(2):402-413.
    PMID: 38287712 DOI: 10.1002/bab.2548
    Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.
  15. Suleman M, Murshed A, Imran K, Khan A, Ali Z, Albekairi NA, et al.
    BMC Chem, 2024 May 11;18(1):99.
    PMID: 38734638 DOI: 10.1186/s13065-024-01185-4
    The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has led to over six million deaths worldwide. In human immune system, the type 1 interferon (IFN) pathway plays a crucial role in fighting viral infections. However, the ORF8 protein of the virus evade the immune system by interacting with IRF3, hindering its nuclear translocation and consequently downregulate the type I IFN signaling pathway. To block the binding of ORF8-IRF3 and inhibit viral pathogenesis a quick discovery of an inhibitor molecule is needed. Therefore, in the present study, the interface between the ORF8 and IRF3 was targeted on a high-affinity carbon nanotube by using computational tools. After analysis of 62 carbon nanotubes by multiple docking with the induced fit model, the top five compounds with high docking scores of - 7.94 kcal/mol, - 7.92 kcal/mol, - 7.28 kcal/mol, - 7.19 kcal/mol and - 7.09 kcal/mol (top hit1-5) were found to have inhibitory activity against the ORF8-IRF3 complex. Molecular dynamics analysis of the complexes revealed the high compactness of residues, stable binding, and strong hydrogen binding network among the ORF8-nanotubes complexes. Moreover, the total binding free energy for top hit1-5 was calculated to be - 43.21 ± 0.90 kcal/mol, - 41.17 ± 0.99 kcal/mol, - 48.85 ± 0.62 kcal/mol, - 43.49 ± 0.77 kcal/mol, and - 31.18 ± 0.78 kcal/mol respectively. These results strongly suggest that the identified top five nanotubes (hit1-5) possess significant potential for advancing and exploring innovative drug therapies. This underscores their suitability for subsequent in vivo and in vitro experiments, marking them as promising candidates worthy of further investigation.
  16. Suleman M, Sayaf AM, Khan A, Khan SA, Albekairi NA, Alshammari A, et al.
    J Infect Public Health, 2024 Jul;17(7):102448.
    PMID: 38815532 DOI: 10.1016/j.jiph.2024.05.005
    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.

  17. Abbas SA, Khan A, Fatima M, Kalusalingam A, Kanakal MM, Inamdar SK, et al.
    PMID: 38357954 DOI: 10.2174/0118715230285370240131111539
    BACKGROUND: Seeds of plant Scaphium affine are traditionally used by the healers of "India" for the treatment of piles.

    OBJECTIVES: The primary objective of the study was to assess the anti-hemorrhoidal potential of the ethanolic seed extract of Scaphium affine.

    METHODS: After the soxhlet extraction method, the seed extract from Scaphium affine was first submitted to phytochemical standardization and then GC-MS analysis. Rats were given Croton oil and Jatropha oil to develop hemorrhoids, and Scaphium affine seed extract (ESA) was administered orally for 5 days and 3 days, respectively, at doses of 1000 and 500 mg/kg. The Rectoanal coefficient (RAC) was calculated as an inflammatory marker. The hemorrhoidal tissues were also subjected to cytokine profiling, biochemical estimation and histopathology.

    RESULTS: ESA demonstrated the presence of flavonoids, saponins, phytosterols, phenols, and tannins. GCMS analysis elucidated the presence of hexadecanoic acid 2 hydroxy -1,3 propane diyl ester,9 Octadecanoic acid ethyl ester, Cyclohexane 1,4 di methyl cis, Farnesol isomer,1, E-11, Z-13 octa decatriene, Stigmasterol, N-(5 ethyl -1,3,4-thiadiazol-yl) benzamide, N, N Dinitro 1,3,5,7 tetraza bicyclo 93,3,1) as major phytoconstituents. The results depicted more potent anti-hemorrhoidal activity of ESA at 1000 mg/kg, p.o., which was evident through a decrease in RAC. A significant decline in the levels of IL-1β, IL-6, and TNF-α expression was observed, along with the restoration of altered antioxidants and enzymes. Histopathological analysis confirmed the tissue recovery as it revealed minimal inflammation and decreased dilated blood vessels in treated animals.

    CONCLUSION: Based on the results it can be concluded that seeds of Scaphium affine showed significant anti-hemorrhoid agents which may be attributed to their anti-inflammatory and anti-oxidant potential due to the presence of certain phytoconstituents in it. The study also supports the traditional use of seeds of Scaphium affine for the first time in the treatment of hemorrhoids.

  18. Kanakal MM, Abbas SA, Khan A, Sultana S, Fatima H, Tabasssum R, et al.
    PMID: 39082166 DOI: 10.2174/0118715230309053240718122527
    INTRODUCTION: This research aims to create a gel formulation of Brassica juncea leaf extract and assess its anti-inflammatory properties using an in silico study. The anti-inflammatory activity has been compared with Diclofenac molecules in PDB id: 4Z69. Further, the Absorption, Distribution, Metabolism, Excretion, and Toxicity analysis has been performed to ensure the therapeutic potential and safety of the drug development process. The Quality by Design tool has been applied to optimize formulation development.

    METHODS: The extracted gel is characterized by performing Fourier transformer infrared, zeta potential, particle size, Scanning Electron Microscope, and entrapment efficiency. Further, the formulation is evaluated by examining its viscosity, spreadability, and pH measurement. An In vitro study of all nine extract suspensions was conducted to determine the drug contents at 276 nm.

    RESULTS: The optimized suspension has shown the maximum percentage of drug release (82%) in 10 hours of study. Animal study for anti-inflammatory activity was performed, and results of all five groups of animals compared the % inhibition of paw edema at three hours; gel (56.70%), standard (47.86%), and (39.72%) were found.

    CONCLUSION: The research could conclude that the anti-inflammatory activity of gel formulation is high compared to extract, and a molecular docking study validates the anti-inflammatory therapeutic effects. ADMET analysis ensures the therapeutic effects and their safety.

  19. Sayaf AM, Kousar K, Suleman M, Albekairi NA, Alshammari A, Mohammad A, et al.
    BMC Chem, 2024 Nov 26;18(1):236.
    PMID: 39593151 DOI: 10.1186/s13065-024-01347-4
    Hypoxia-inducible factors (HIFs) are transcription factors that regulate erythropoietin (EPO) synthesis and red blood cell (RBC) production. Prolyl-4-hydroxylase domain (PHD) enzymes are key regulators of HIF's stability and activity. Inhibiting PHD enzymes can enhance HIF-mediated responses and have therapeutic potential for diseases such as anemia, cancer, stroke, ischemia, neurodegeneration, and inflammation. In this study, we searched for novel PHD inhibitors from four databases of natural products and synthetic compounds: AfroDb Natural Products, AnalytiCon Discovery Natural Product (NP), HIM-Herbal Ingredients In-Vivo Metabolism, and Herbal Ingredients' Targets, with a total number of 13,597 compounds. We screened the candidate compounds by molecular docking and validated them by molecular dynamics simulations and free energy calculations. We identified four target hits (ZINC36378940, ZINC2005305, ZINC31164438, and ZINC67910437) that showed stronger binding affinity to PHD2 compared to the positive control, Vadadustat (AKB-6548), with docking scores of - 13.34 kcal/mol, - 12.76 kcal/mol, - 11.96 kcal/mol, - 11.41 kcal/mol, and - 9.04 kcal/mol, respectively. The target ligands chelated the active site iron and interacted with key residues (Arg 383, Tyr329, Tyr303) of PHD2, in a similar manner as Vadadustat. Moreover, the dynamic stability-based assessment revealed that they also exhibited stable dynamics and compact trajectories. Then the total binding free energy was calculated for each complex which revealed that the control has a TBE of - 31.26 ± 0.30 kcal/mol, ZINC36378940 reported a TBE of - 38.65 ± 0.51 kcal/mol, for the ZINC31164438 the TBE was - 26.16 ± 0.30 kcal/mol while the ZINC2005305 complex reported electrostatic energy of - 32.75 ± 0.58 kcal/mol. This shows that ZINC36378940 is the best hit than the other and therefore further investigation should be performed for the clinical usage. Our results suggest that these target hits are promising candidates that reserve further in vitro and in vivo validations as potential PHD inhibitors for the treatment of renal anemia, cancer, stroke, ischemia, neurodegeneration, and inflammation.
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