Background: Growing diabetes prevalence prompts investigation into plant-derived compounds’ potential to inhibit α-amylase, offering novel therapeutic avenues for treating diabetes mellitus (DM). Purpose: In the current study, ethanolic and methanolic extracts of Fagonia cretica and Berberis lycium were evaluated against α-amylase. Methods: The inhibitory activity of ethanolic and methanolic extracts was analyzed based on their IC50 values. An in vitro activity of α-amylase inhibition was performed, followed by molecular docking and molecular dynamics (MD) simulation of selected compounds. Results: Results indicated that F. cretica and B. lycium extracts have strong inhibitory effects against α α-amylase. In ethanolic and methanolic extracts, the methanolic B. lycium extract was the most potent with an IC50 value of 2.10 µg/mL; the ethanolic B. lycium, ethanolic, and methanolic F. cretica extracts also showed significant anti-α-amylase effects with IC50 values of 3.88, 4.09, and 7.26 µg/mL, respectively. Further, a total of 36 phytochemicals were docked against the α-amylase enzyme to explore the binding mode of these phytochemicals. Docking results confirmed that most of the phytochemicals accommodate well in the active site of α-amylase and made strong interactions compared to the standard drug acarbose. Also, the MD simulation results confirmed that both phytochemicals revealed greater stability than the standard acarbose. Conclusion: Based on these results, we concluded that the extract showed good effectiveness and further in vivo study is needed to manage DM.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed substantial challenges on our society due to the COVID-19 pandemic. This virus relies heavily on its surface glycoprotein (S-glycoprotein) to facilitate attachment, fusion, and entry into host cells. While the nucleoprotein (N) in the ribonucleoprotein core binds to the viral RNA genome. Therefore, our objective is to develop a novel vaccine candidate targeting the dominant T-cell and B-cell epitopes of the immune system. On the S-glycoprotein and nucleoprotein. Employing an immunoinformatic approach, we constructed a vaccine candidate with 13 highly antigenic B-cell epitopes, 19 HTL antigenic epitopes, and 18 CTL epitopes following a rigorous assessment. The multi-epitope construct successfully passed three-fold toxicity, allergenicity, and antigenicity tests, affirming its non-toxic, non-allergenic, and antigenic nature. This demonstrates the potentiality of the vaccine design to trigger an immunological response. Furthermore, the vaccine-ACE-2 receptor complex was tested, confirming its ability to interact with ACE-2’s core pocket and induce an immunological response. Additionally, the vaccine’s binding prowess for human toll-like receptors (TLR) (1, 3, 4, and 8) was investigated. According to the Ramachandran plot, 77.46% of the construct’s amino acid residues fall within a favorable zone, establishing it as a viable vaccine candidate.

Human rhinovirus C (HRV-C) is a significant contributor to respiratory tract infections in children and is implicated in asthma exacerbations across all age groups. Despite its impact, there is currently no licensed vaccine available for HRV-C. Here, we present a novel approach to address this gap by employing immunoinformatics techniques for the design of a multi-epitope-based vaccine against HRV-C. The sequences of the chosen structural proteins VP1 and VP2, along with the non-structural protein 2C of HRV-C, were downloaded in FASTA format from the NCBI server for further analysis. Through an exhaustive analysis of HRV-C genomic sequences, we identified highly conserved immunogenic regions capable of eliciting a protective immune response. Leveraging advanced immunoinformatics tools, we predicted epitopes for B-cells, Cytotoxic T lymphocytes, and Helper T lymphocytes, ensuring broad coverage across different HRV-C strains. The vaccine candidate was constructed by integrating selected antigens with immunogenic epitopes and adjuvants, employing optimal linkers. Three vaccine constructs were developed, with V2 being the most promising, consisting of 480 amino acids residues. V2 exhibited strong antigenicity, non-allergenicity, and solubility, with a solubility score greater than 0.550, and demonstrated excellent structural stability, with 91.9% of residues in the most favorable regions of the Ramachandran plot. Molecular dynamics and simulation studies revealed a stable Vaccine-TLR8 complex, with a binding energy of -296.15 and consistent RMSD values. Furthermore, in silico cloning and sequence optimization ensured efficient expression in E. coli, with a Codon Adaptation Index of 0.99 and GC content of 54.58%. The minimum free energy of the RNA secondary structure was -494.90 kcal/mol. While our findings suggest the potential effectiveness of the designed vaccine candidate against HRV-C, further in vitro and in vivo investigations are warranted to validate its safety and efficacy.

Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) is pneumonia like viral disease which was originated from Wuhan China in 2019. Besides its high morbidity and mortality, a lot of physiological, enzymatic, hormonal and genetic imbalances had also been observed among Corona Virus Disease-19 (COVID-19) patients. The purpose of the present study was the assessment of comorbidities and association of single nucleotide polymorphisms (SNPs) in Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine (TMPRSS) gene among COVID-19 patients. A total of 300 (healthy control n = 150 COVID-19 n = 150) individuals were sampled and genotyped for ACE2 rs2285666 and TMPRSS rs2070788 SNPs respectively. A total of 92/150 (61.3

Polycystic ovarian syndrome is a heterogeneous endocrine disorder characterized by ovarian cysts, anovulation, endocrine variations, which includes oligo-amenorrhea along with associated subfertility and hyperandrogenism manifested as acne, hirsutism, and male-pattern alopecia. Coumarins are fused benzene and pyrone ring systems that exhibit a wide spectrum of bioactivities. This study aimed to investigate the effects of 3-acetyl coumarin (3-AC) on polycystic ovarian syndrome in female rats. Acute oral toxicity conducted according to OECD guidelines 425 (a test conducted in scenarios where there is information indicating that the test material is non-toxic) exhibited no mortality. In vitro DPPH assay demonstrated anti-oxidant potential of 3-AC. Letrozole, a nonsteroidal aromatase inhibitor was used to induce PCOS (1 mg/kg-21 days). Normal and PCOS control rats were administered a vehicle solution (0.5

Various metabolic and cell signaling processes impact the functions of sugarcane plant cells. MicroRNAs (miRNAs) play critical regulatory roles in enhancing yield and providing protection against various stressors. This study seeks to identify and partially characterize several novel miRNAs in sugarcane using in silico tools, while also offering a preliminary assessment of their functions. This was accomplished by predicting novel conserved miRNAs in sugarcane plants using a variety of genomics-based techniques like BLASTn, MFOLD, psRNA Target, sequence logo, Weblogo, primer-3, etc. and annotated using miRBase and NCBI. For validation, RT-PCR method was used along with agarose gel. After the preparation of fourteen randomly chosen primers, they were validated by RT-PCR. Accordingly, they contain fifty specific targeted proteins with substantial targets in the structural, transcriptional protein, etc. Furthermore, the sof-miR5025a directs the heat repeat protein while the voltage-dependent anion is governed by sof-miR8005a. Similarly, the sof-miR7768b and sof-miR6249b monitor the pathogenesis-related protein and zinc finger, C2H2 type protein, which assist as transcription factors. Thus, the novel sugarcane miRNAs target a wide range of important genes help regulate the environment for sugarcane to generate a higher-quality crop.

The aim of this study was to develop a ciclopirox (CXP) topical nano spray using nanotechnology to enhance drug bioavailability and skin absorption. A precipitation method was employed to incorporate CXP in its nano particulate form, using chitosan as the polymer. Chitosan nanoparticles (CT NPs) possess unique properties that make them highly suitable for biological applications. The study focused on investigating the penetration behavior of chitosan nanoparticles (nano spray) through artificial skin, with the goal of developing them as effective skin delivery systems for medications. The nanoparticles had an average size of 640 nm, with a positive or negative surface potential and a polydispersity index (PDI) of 0.298. A thorough analysis of the nano spray was conducted using several scientific techniques, including X-ray diffractometry, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), as well as in vitro release and diffusion studies. Additionally, cell viability was evaluated using the MTT assay, and blood compatibility was tested through a hemolysis test. The study also assessed the levels of the anti-inflammatory cytokine IL-2 in the lungs of mice using RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR). The drug dissolution and diffusion rates showed a significant improvement compared to the pure reference sample. Therefore, the CXP nano spray appears to be an efficient and practical method to enhance skin penetration, bioavailability, and permeability. Based on the results, the CXP nano spray holds potential as a promising treatment for fungal infections, particularly for skin diseases.

Food safety is a critical issue in the 21st century due to antibiotic-resistant bacteria causing harmful foodborne diseases. This comprehensive study meticulously examined the presence of bacterial isolates, quinolone residue, and antimicrobial resistance genes in samples of broiler and fish meat. Forty samples were collected from various locations in the Faisalabad metropolis. The samples underwent culture on various types of agar, and the Vitek 2 compact system was used to confirm the isolates along with determining the minimum inhibitory concentration of antibiotics. Additionally, polymerase chain reaction was used to identify antimicrobial-resistant genes, and an enzyme-linked immunosorbent assay (ELISA) kit was employed to detect quinolone residue in each sample. Out of 40 fish samples, 66 polymicrobials were identified with Escherichia coli being the most prevalent (26.6%), followed by Klebsiella pneumoniae (16.6%) and Acinetobacter baumannii (15%). Furthermore, 70 polymicrobial were identified in the broiler samples, with 41.6% E. coli and 15% K. pneumoniae. In fish isolates, 14 (21%) qnr gene, 18 (27.2%) blaCTX-M, and 11 (16.6%) blaNDM-1, and in broiler samples, 19 (27.1%) qnr gene, 19 (27.1%) blaTEM and 22 (31.4%) blaCTX-M, and 5 (7.1%) blaNDM-1 were found. Eighteen (45%) broiler and 7 (17.5%) fish samples with more than 100 µg per kg (ppb) for quinolone residues. The study concluded that the increased prevalence of multidrug-resistant bacteria and quinolone residue poses a significant threat to consumer health.

This study presents the fabrication and characterization of mixed matrix membranes (MMMs) incorporating green-synthesized silver nanoparticles (AgNPs) using Hibiscus Rosa sinensis extract within a polyethersulfone (PES) matrix for nanofiltration (NF) application. The membranes were evaluated for their pure water permeability, salt rejection, dye removal, and antifouling performance. Results showed that the membrane with 0.75 wt% AgNPs exhibited the highest pure water permeability of 36 L/m2 h−1 bar−1 attributed to increased porosity and enhanced hydrophilicity. Addition of 0.75wt% AgNPs resulted in significant improvements, with NaCl rejection increased from 32 to 57%, MgSO4 from 26 to 67%, and CaCl2 from 27 to 41%. Antifouling tests revealed that the 0.75 wt% AgNPs membrane had the lowest irreversible fouling and highest flux recovery due to the antimicrobial action and improved surface properties of AgNPs. Importantly, the performance of the fabricated membranes align with loose nanofiltation characteristcs, as evidence by high dye rejection rates coupled with moderate rejection of salts. This study highlights the potential of green-synthesized AgNPs as effective nanofillers for developing high-performance and environmentally sustainable membranes into wastewater treatment.

Introduction Heterogeneous Acute Myeloid Leukemia (AML) causes substantial worldwide morbidity and death. AML is characterized by excessive proliferation of immature myeloid cells in the bone marrow and impaired apoptotic regulator expression. B-Cell Lymphoma 2 (BCL-2), an anti-apoptotic protein overexpressed in AML, promotes leukemic cell survival and chemoresistance. Thus, reducing BCL-2 may treat AML. Anticancer activities are found in Aloe barbadensis Miller (Aloe vera). Thus, this work used molecular modeling to assess Aloe vera bioactive chemicals as BCL-2 inhibitors. Methods Selected bioactive compounds from Aloe vera was docked against BCL-2 using AutoDock Vina. drug-likeness, pharmacokinetics, and toxicity profiling was carried out using SwissAdme and ADMETSar servers. Finally, the two most promising compounds were subjected to 100 ns molecular dynamics (MD) simulation in Desmond software. Results The Binding energies of the compounds were found to be between -6.7 to -8.7 kcal/mol, with campesterol and a-tocopherol returning the least binding energy. Furthermore, both compounds displayed good druglikeness, and ADMET profiles. In addition, they maintained stable nature in the binding pocket of BCL-2 during the 100 ns MD simulation. Conclusion Campesterol and α-tocopherol are promising BCL-2 inhibitors that might become effective anti-leukemic therapies with additional in vitro and in vivo research.

The objective of this study was to explore how watermelon rinds (WMRs) and their derivatives, specifically water-soluble polysaccharides (WMRPs) and hemicellulose (WMRH), as sources of dietary fiber, could enhance the quality of wheat bread. The extraction process yielded 34.4% for WMRP and 8.22% for WMRH. WMR, WMRP, and WMRH exhibited promising functional characteristics and were incorporated separately into wheat flour with low bread-making quality (FLBM) at varying proportions (0.5%, 1%, and 1.5% (w/w)). The volume, texture, and crust and crumb color underwent evaluation and were compared to the control. The findings indicated that incorporating WMR notably enhanced the alveograph profile of the dough, demonstrating a more effective impact than the addition of WMRP and WMRH. Adding WMR, WMRP, and WMRH at a 1% concentration to low-quality wheat flour for bread making increased the deformation work values by 16%, 15%, and 13%, respectively, and raised the P/L ratios by 42%, 36%, and 38%, respectively. Additionally, the assessment of the bread highlighted a substantial enhancement in both volume and texture profile when WMR was added, in contrast to the control bread (made with FLBM). These findings underscore that incorporating 1% WMR into FLBM was the most effective means of improving bread quality based on the results of this study.

Background: Juniperus turbinata Guss. is a medicinal mountain plant used by the Indigenous population in the traditional pharmacopeia. Purpose This study aimed at investigating the phytochemical analysis, antimicrobial, antioxydant and hymolytic activities of Juniperus turbinata Guss. leaves extracts. Materials and Methods The essential oils of Juniperus turbinata Guss. (EOJL) leaves were extracted, and their phytochemical composition was characterized by gas chromatography-mass spectrometry (GC-MS). EOJL was evaluated for its anti-free radical (2,2-diphenylpicrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and total antioxidant capacity (TAC)) properties, as well as antibacterial, antifungal, and hemolytic activities. Results The chemical study showed that EOJL contains 14 chemicals, with a 99.98% identification rate. The most abundant compounds in EOJL are linalool (45%), borneol (12%), and cineole (11%). The EOJL exhibited a 50% inhibition concentration of DPPH radicals value of 23.56 +/- 0.72 mu g/mL (DPPH) for its antioxidant activity, an effective concentration equivalent of 0.50 nm value of 239.08 +/- 5.13 mu g/mL (FRAP), and a total antioxidant activity of 735.03 +/- 21.25 mu g AAE/mg (TAC). The antibacterial efficacy of EOJL on a solid substrate demonstrated a range of 10-15 mm in diameter for bacterial strains, 14.33 +/- 1.15 mm for C. albicans, and 56.68 +/- 1.19% for Fusarium oxysporum. The bacterial strains exhibited a minimum concentration range of 6.15-11.26 mu g/mL on the solid medium, whereas the range for the strains was between 5.11 and 10.23 mu g/mL. The molecular docking analysis demonstrated that terpineol has potent antioxidant activity against NADPH oxidase, as shown by a shift score of -4.055 kcal mol-1. Eugenol also showed significant antioxidant activity with a shift value of -4.003 kcal mol-1. Camphor exhibited significant efficacy against S. aureus nucleoside diphosphate kinase, as demonstrated by a slip score of -5.156 kcal mol-1. Conclusion The findings highlight the significance of EOJL as a natural antioxidant and its antibacterial potential against pathogenic strains that are therapeutically relevant.

Transforming growth factor beta 1 (TGF-beta) is a cytokine with pleiotropic biological functions. Recently, its signaling pathway has been highlighted for its implicative paradoxical roles in prostate cancer (PCa). Suppressing downstream effects of this pathway by interfering with receptor complex formation through inhibition of the TGF-beta 1 leads to its antitumor effects, illuminating the TGF-beta 1 as a viable therapeutic target for PCa. Our compound library-established by a literature-based approach that identified phytochemicals with published evidence against the TGF-beta 1-was screened by employing molecular docking, density functional theory (DFT), and molecular dynamic (MD) simulations to identify TGF-beta 1 inhibitors. Eight of the 24 phytochemicals docked from our compound library had a good binding affinity (ranging from -11.7 to -10 kcal/mol) to the TGF-beta 1 (PDB: 1PY5). The phytochemicals displayed good stability and reactivity as revealed by the DFT analysis and a desirable pharmacokinetic profile. The top four phytochemical complexes with high binding energies maintained stability throughout the 100 ns simulation. Qualitative studies on the drug repurposing attributes of bisindolylmaleimide, flavopiridol, baicalin, and gefitinib as inhibitors of TGF-beta 1 are recommended; most importantly, suggest further wet-lab studies to corroborate these phytochemicals-SB 202190, SB 203580, silymarin, and cryptotanshinone-in TGF-beta 1 targeted drug development.

Breast cancer has rapidly increased in prevalence in recent years, making it one of the leading causes of mortality worldwide. Among all cancers, it is by far the most common. Diagnosing this illness manually requires significant time and expertise. Since detecting breast cancer is a time-consuming process, preventing its further spread can be aided by creating machine-based forecasts. Machine learning and Explainable AI are crucial in classification as they not only provide accurate predictions but also offer insights into how the model arrives at its decisions, aiding in the understanding and trustworthiness of the classification results. In this study, we evaluate and compare the classification accuracy, precision, recall, and F1 scores of five different machine learning methods using a primary dataset (500 patients from Dhaka Medical College Hospital). Five different supervised machine learning techniques, including decision tree, random forest, logistic regression, naive bayes, and XGBoost, have been used to achieve optimal results on our dataset. Additionally, this study applied SHAP analysis to the XGBoost model to interpret the model’s predictions and understand the impact of each feature on the model’s output. We compared the accuracy with which several algorithms classified the data, as well as contrasted with other literature in this field. After final evaluation, this study found that XGBoost achieved the best model accuracy, which is 97%.

Domestic yak ( Bos grunniens ) is an economically important feature of the mountainous region of Gilgit-Baltistan in Pakistan where agriculture is restricted and yaks play multiple roles which includes being a source of milk, meat, hides, fuel and power. However little is known about the parasitic infections in Pakistani yaks. Aim of this research was to report the prevalence and genetic diversity of protozoa parasite (Theileria ovis, 18 S rDNA gene was targeted) and an obligate bacterium (Anaplasma marginale, msp-1 gene was amplified) in the blood that was sampled from 202 yaks collected from four districts in Gilgit-Baltistan during January 2023 till January 2024. Results revealed that 6/202 (3%) yaks were of Theileria ovis while 8/202 (4%) were Anaplasma marginale infected. Positive PCR products of both parasites were confirmed by DNA sequencing and their similarity with previously available pathogen sequences was determined by BLAST analysis. Phylogenetic tree indicated that isolates of both parasites displayed genetic. Anaplasma marginale infection varied with the sampling districts and Shigar district had the highest rate of bacterial infection. Cows were significantly more prone to Theileria ovis infection than bulls. Calf and hybrid yaks were more prone to Anaplasma marginale infection. In conclusion, this is the first report that yaks residing the Gilgit-Baltistan region in Pakistan are infected with Theileria ovis and Anaplasma marginale . Similar larger scales studies are recommended in various regions of Gilgit-Baltistan to document the infection rates of these parasites to formulate strategies that will lead to the effective control of these pathogens.

The present study deals with the bio-fabrication of AgA-AgNPs utilizing edible mushroom Agaricus arvensis as a reductant for improved stability and catalytic efficiency towards L-dopa production. The parameters optimized for achieving maximum tyrosine hydroxylase (TH) activity were the mushroom biomass (2.5%, w/v), media for extraction (peptone-saline), and temperature (90 ℃). The activity of tyrosine hydroxylase (TH) was enhanced by its immobilization on AgNPs. The change in color from light yellow to dark brown confirmed the formation of AgA-AgNPs. In addition, the UV–Vis spectrum showed a surface plasmon resonance band at 260 nm. Fourier transform infrared (FTIR) indicated presence of functional groups, which play an important role in production of NPs. X-ray diffraction (XRD) confirmed the crystalline nature of mycosynthesized AgNPs and showed peaks corresponding to 38.8° (111), 46.5° (200), 64.1° (220), and 77.5o (311). AgA-AgNPs exhibited −9.16 mv zeta potential. Scanning Electron Microscopy (SEM) images of AgA-AgNPs confirmed particle size between 88.49 ± 3.83 nm. Immobilized TH extracted from A. arvensis showed reusability at optimized temperature (20 ℃) for 3 cycles. A 2.54-fold higher production of L-dopa was examined with AgA-AgNPs. Furthermore, immobilized TH consumed more L-tyrosine i.e. 0.554 ± 0.022 mg/ml as compared to the free enzyme at 90 min of biotransformation. Hence, the immobilization of A. arvensis extracted TH on AgNPs increased its activity as well as its stability and catalytic efficiency. AgA-AgNPs has a potential of dopamine synthesis and can play a significant role in drug delivery or biomedical applications.

Fluorescent Carbon Quantum Dots (CQDs) are being used in medical applications, particularly in theranostics. These Carbon Quantum Dots have been gaining more attention lately due to their potential as an effective replacement for hazardous synthetic organic dyes in a variety of biomedical applications, including live cell imaging and diagnostics. In this study, highly fluorescent Carbon Quantum Dots by one pot microwave based green route with a size of less than 10 nm, was prepared from commercially available almond resin, Prunus dulcis and conjugated with honey as additional reagent for surface functionalization. They exhibit a deep blue emission on excitation at 350 nm with an elevated quantum yield at 61%. They possess atomic nature and basic features such as high photo-stability, varying fluorescence, greater biocompatibility, and better water solubility. These fluorescent labels exhibit faster cellular invagination without disturbing the cell stability. The CQDs present cell imaging capacity with multi-coloration for visualizing the fine architecture of the nucleus naming, the nuclear membrane and nucleolus, which is linked with their varied, surface structures such as amphiphilic property and higher positive charges. These characteristics with minimal invasion have made carbon quantum dots to become the spotlight in theranostics. They can be used as alternatives to synthetic dyes for fluorescence- related cell-imaging. The intriguing fact about this approach is that it opens the possibility of combining therapy and diagnostics into one unit, which can alter how some diseases are handled and, in turn, transform the field of healthcare.

In the last few decades, researchers have thoroughly studied the use of plants in Palestine, one of them is Cyclamen persicum Mill. (C. persicum). Cyclamen persicum has been historically cultivated since the 1700s due to its tuber. The tuber is known to stimulate the nasal receptors, thus triggering the sensory neurons. Cyclamen persicum has anti-inflammatory effects, reduces cholesterol levels, treats diabetes, and inhibits tumor growth. In this respect, in-vitro examination of antibacterial and anticancer activities and antioxidative potency of C. persicum ethanolic extract were evaluated. The antioxidative potency of the extracted plant material was determined spectrophotometrically using the DPPH free radical scavenging method and the HPLC-PDA method to evaluate its total phenolic content (TPC) and total flavonoid content (TFC). The experimental results revealed weak antibacterial activity of C. persicum extract against both gram negative (E. coli) and gram positive (Streptococcus aureus and S. aureus) bacterial strains, with the zones of inhibition found to be less than 8 mm. On the other hand, powerful activity against MCF7 breast cancer as well as HT29 colon cancer cell lines was obtained. The findings also revealed potent inhibition of free radicals and the presence of maximal levels of natural products such as phenolic compounds and flavonoids, which supportits biological activities and powerful ability to scavenge free radicals. HPLC results showed the presence of numerous flavonoid and phenolic compounds such as rutin, chlorogenic acid, kaempferol, trans-cinnamic acid, quercetin, sinapic acid, and p-coumaric acid.

Effervescent formulation helps in faster and better absorption of drugs, especially those that are rapidly soluble in water. However, these tablets require special packaging in order to prevent them from absorbing moisture, hence increasing cost. We compared an effervescent tablet prepared using an in-house developed method (multi-layer tablet with acid and base part separated by an inert layer) to a European effervescent tablet (Efferalgan®) in a single-center, randomized cross-over study among twelve healthy volunteers. Blood samples were collected for 8 h and analyzed for paracetamol concentration using HPLC. Our results showed that both the products have similar pharmacokinetic profiles with no significant difference observed for Clast, Thalf, Kelim, and MRT (p-value > 0.05). Moreover, to assess bioequivalence we did not find any significant difference (p-value > 0.05) in AUC (27.12 ± 6.02 vs. 27.29 ± 2.64 µg.h/ml), Cmax (7.42 ± 1.06 vs. 7.83 ± 1.19 µg/ml) and tmax (0.85 ± 0.22 vs. 0.83 ± 0.25 h). The TR ratios for AUC, Cmax, and tmax were 0.99, 0.95, and 1.02 respectively, and were all within the specified FDA limits i.e., 0.8–1.25. We found our test tablet to be bioequivalent to that of Efferalgan®.

The pharmacological effects of limonene, especially their derivatives, are currently at the forefront of research for drug development and discovery as well and structure-based drug design using huge chemical libraries are already widespread in the early stages of therapeutic and drug development. Here, various limonene derivatives are studied computationally for their potential utilization against the capsid protein of Herpes Simplex Virus-1. Firstly, limonene derivatives were designed by structural modification followed by conducting a molecular docking experiment against the capsid protein of Herpes Simplex Virus-1. In this research, the obtained molecular docking score exhibited better efficiency against the capsid protein of Herpes Simplex Virus-1 and hence we conducted further in silico investigation including molecular dynamic simulation, quantum calculation, and ADMET analysis. Molecular docking experiment has documented that Ligands 02 and 03 had much better binding affinities (- 7.4 kcal/mol and - 7.1 kcal/mol) to capsid protein of Herpes Simplex Virus-1 than Standard Acyclovir (- 6.5 kcal/mol). Upon further investigation, the binding affinities of primary limonene were observed to be slightly poor. But including the various functional groups also increases the affinities and capacity to prevent viral infection of the capsid protein of Herpes Simplex Virus-1. Then, the molecular dynamic simulation confirmed that the mentioned ligands might be stable during the formation of drug-protein complexes. Finally, the analysis of ADMET was essential in establishing them as safe and human-useable prospective chemicals. According to the present findings, limonene derivatives might be a promising candidate against the capsid protein of Herpes Simplex Virus-1 which ultimately inhibits Herpes Simplex Virus-induced encephalitis that causes interventions in brain inflammation. Our findings suggested further experimental screening to determine their practical value and utility.