Biology subjects

Rahman, M. A.

Publications and source records attributed to Rahman, M. A..

At least 19 recordsLinked to original sources

bioRxiv2026

CRISPR-mediated Correction of Oncogenic AS-NMD in Splicing Factor Mutant Cancer

Alternative splicing coupled to nonsense-mediated mRNA decay (AS-NMD) evolved as a master regulator of gene expression. Dysregulated AS-NMD has been identified as the root of many human maladies, from developmental defects to deadly cancer. Poison exons (PEs) are highly conserved alternative exons that contain a premature termination codon and elicit AS-NMD when included in a transcript. Cancer cells often exploit the inclusion of PEs to downregulate tumor suppressors or the exclusion of PEs to upregulate oncoproteins. Therefore, PEs have drawn significant attention as a novel therapeutic avenue for cancer and other diseases. Here, we examine a therapeutic proof-of-concept for manipulating PE-mediated oncogenic AS-NMD using a CRISPR-based approach. Using paired guide RNA, we successfully deleted a PE of a tumor suppressor (EZH2) from the genome of SRSF2-mutated leukemia. This editing resulted in EZH2 mRNAs without a PE, escaped AS-NMD, and restored the protein expression. This subsequently reinstated H3K27 histone methylation and rescued defective chromatin regulation associated with impaired hematopoietic stem cell differentiation. Finally, we showed the preferential advantages of CRISPR over the antisense technology we recently developed targeting the PE of EZH2. Therefore, the CRISPR strategy shows compelling evidence as a therapeutic approach targeting PE in cancer and other human diseases.

cancer biology↗

bioRxiv2026

VESTA: Machine Learning-Enabled Estimation of ViscoElastic Ratios from On-Axis Spatio-Temporal ARFI Features

Viscoelastic characterization of tissue has significant diagnostic value in oncology, as tumor progression alters both elasticity and viscosity in ways that neither property alone can fully capture. Existing acoustic radiation force (ARF)-based methods such as Viscoelastic Response (VisR) ultrasound estimate relative elasticity and viscosity through per-A-line nonlinear model fitting, which is computationally intensive and requires auxiliary simulations to correct elasticity-dependent bias. This work presents VESTA (Machine Learning-Enabled Estimation of ViscoElastic Ratios from On-Axis Spatio-Temporal ARFI Features), a two-stage data-driven pipeline that predicts elasticity ratio (ER) and viscosity ratio (VR) directly from seven normalized ARFI displacement features at the A-line level, without model fitting or compensation. Stage 1 is an MLP classifier that detects inclusion boundaries from normalized peak displacement and negative peak velocity ratios; Stage 2 is a dilated Conv1D regression model that estimates ER and VR along the full axial sequence using the predicted mask alongside displacement features. The pipeline was trained on 500 simulated inclusion scenarios spanning three geometries, five focal depths, two F-numbers, and a broad range of material contrasts. In silico, mean predicted ER and VR were within 12% of ground truth across all geometries, with performance best when ER and VR were moderate or decoupled. Experimental validation on a chicken breast phantom demonstrated plausible generalization to real tissue heterogeneity. Applied to an in vivo murine 4T1 breast cancer model, the pipeline tracked treatment-related attenuation of mechanical contrast in paclitaxel-treated tumors relative to controls over a 36-day imaging period, supporting its relevance for tumor monitoring.

bioengineering↗

bioRxiv2026

Cross-Cancer Profiling of Cadherin-1 Reveals Context-Dependent Epithelial-Mesenchymal Transition Decoupling, Immune Heterogeneity, and Prognostic Variability in Epithelial Cancers

BackgroundCDH1 (E-cadherin) is a key epithelial adhesion molecule traditionally associated with tumor suppression and epithelial-mesenchymal transition (EMT). However, its roles across cancers remain incompletely understood, particularly within multilayer regulatory contexts involving genomic, epigenetic, transcriptional, and immune mechanisms. MethodsCDH1 expression, survival associations, EMT-correlated gene profiles (VIM, SNAI1, ZEB1), immune infiltration patterns, immune checkpoint correlations (PDCD1, CD274, CTLA4), promoter methylation, and genomic alterations were assessed across five epithelial cancers, breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD), ovarian cancer (OV), and stomach adenocarcinoma (STAD). Cross-platform validation was performed using TCGA/GDC datasets, GEPIA2, UALCAN, TIMER, KM Plotter, cBioPortal, and g:Profiler. ResultsCDH1 was overexpressed but showed variable prognostic significance; higher expression predicted better survival in COAD, LUAD and STAD, worse survival in BRCA and had no impact in OV. Classic inverse relationships between CDH1 and VIM or ZEB1 were evident only in STAD, and SNAI1 showed no consistent association. Immune infiltration patterns were tumor-specific, ranging from cytotoxic T-cell dominance in LUAD to macrophage-rich profiles in OV; immune checkpoint correlations were similarly context-dependent. Co-expressed genes were enriched for endomembrane transport rather than adhesion pathways. Promoter methylation patterns varied by cancer, whereas genomic alterations of CDH1 were rare. ConclusionsCDH1 does not function as a universal epithelial or EMT marker across epithelial cancers. Instead, its associations with EMT, immune contexture, methylation, and prognosis are context-dependent, supporting a model of CDH1 as a heterogeneous regulator of epithelial plasticity. These findings challenge single-function interpretations and support cancer-specific CDH1 evaluation in translational research.

cancer biology↗

bioRxiv2026

Global Proteomics Investigation of SAMT-247 Targets: An Antiviral Thioester that Acetylates Zinc Finger Proteins

Covalent modification of target proteins is a well-established mechanism of action for small molecule inhibitors. Cysteine residues in particular have been exploited for their reactivity toward electrophilic molecules. SAMT-247 is a mercaptobenzamide thioester that covalently acetylates cysteines in the zinc-coordinating domains of the HIV nucleocapsid protein. This SAMT-247-promoted reaction leads to loss of zinc binding by the protein, with concomitant loss of protein structure and function. Although it has low cytotoxicity in animal models, recent studies have indicated that it affects other protein targets in uninfected cells, for example leading to increased immune cell functions. In this study, global proteomics approaches have been used to better understand other protein targets of SAMT-247. Minimal effects are observed when unstimulated THP-1 monocyte cells were treated with SAMT-247. In contrast, thermal proteome profiling identified 170 proteins with altered thermal stability when THP-1 cells were stimulated with phorbol 12-myristate 13-acetate/Ionomycin (PMA/Iono) before SAMT-247 treatment. Among the affected proteins, 81 contain a zinc-coordinating domain and/or have been shown to have a reactive cysteine residue. Among these, several play a role in cellular metabolism, and Seahorse assays demonstrated that SAMT-247 significantly increased the anti-metabolic and pro-glycolytic effect of PMA/Iono in THP-1 cells. Two of the most-affected proteins were ZC3H7A, a microRNA-binding protein with four zinc finger domains, and MGMT, a DNA damage repair protein with a reactive cysteine. Both proteins were modified by SAMT-247 when tested alone or in the presence of THP-1 cell lysate, indicating that they are bona fide targets of the inhibitor. The low activity of SAMT-247 in unstimulated THP-1 cells is consistent with its low cytotoxicity. The increased effects of SAMT-247 in stimulated immune cells suggests that this molecule could be developed to target diseases other than HIV.

cell biology↗

bioRxiv2026

Targeting EZH2 Oncogenic Splicing: Decoding the Regulatory Network and Antisense Correction

Recurrent mutations in splicing factors (SFs) have been established as crucial drivers of tumorigenesis in several types of blood cancer, and also common in a variety of solid tumors. Mutations change the RNA-binding preferences of SFs, promote global splicing alterations, and often generate erroneous mRNAs that are then degraded by nonsense-mediated mRNA decay (NMD). Consequently, several critical genes linked to hematopoiesis are dysregulated, leading to blood cancer. Although the field has progressed considerably in identifying aberrant genes and affected pathways, effective therapies have not yet emerged in SF-mutated cancers. To address this key gap, we instigated a gene-specific targeted strategy by unlocking the regulatory network. As a proof-of-concept, we scrutinized a tumor suppressor gene EZH2, which is a bona fide target in SRSF2-mutated cancer. We precisely defined splicing cis-elements in EZH2 transcripts and illustrated the dynamic choreography of regulatory proteins in the entire splicing and NMD catalytic pathways. We uncovered a highly coordinated cross-regulation between splicing and NMD promoted by mutant SRSF2 by enhancing the deposition of critical spliceosome- and NMD-associated factors, augmenting mRNA decay to ablate tumor suppression. We then designed antisense oligonucleotides (ASOs) targeting important regulatory sites. Our lead ASO successfully corrects aberrant splicing and NMD, restores the expression and function of EZH2, and partially rescues hematopoietic defects and cellular properties. Our study demonstrates that ASO pharmacology is an actionable strategy for clinical development, challenging the existing paradigms in SF-mutated cancers.

cancer biology↗

bioRxiv2025

APDeeM: A machine Learning strategy towards Effective Peptide Vaccine Candidates Identification against Different Types of Viruses

Viral infections pose significant global health challenges, underscoring the urgent need for improved medications. Nevertheless, traditional medicinal approaches depend significantly on labor-intensive laboratory tests, which impede efficient identification and prolong vaccine development, particularly when screening a huge number of samples. To address these obstacles, we present a comprehensive Antiviral Peptide (AVP) Detection Dataset, comprising 14 unique features to improve the characterization of antiviral and non-antiviral peptides. Subsequently, we introduce the Antiviral Peptide detection enhanced by Ensemble Machine Learning (APDeeM) system. This advanced computational framework considerably reduces the time required for AVP detection by utilizing ensemble learning methodologies. The APDeeM system incorporates Gradient Boosting, Random Forest, K-Nearest Neighbors (KNN), and AdaBoost algorithms to facilitate the swift selection of AVP candidates without requiring urgent laboratory testing. Our proposed ensemble methodology showed superior performance, with an accuracy of 85.99%, F1 score of 87.60%, recall of 88.91%, and precision of 86.32%, exceeding the efficacy of all tested antiviral peptide prediction models in this research. The APDeeM approach signifies a substantial improvement over conventional detection techniques, expediting the identification of prospective vaccine candidates and facilitating the advancement of more effective antiviral peptides. The most promising AVP candidates may urge laboratory validation, optimize resources, and accelerate vaccine development.

bioinformatics↗

bioRxiv2025

Serosurveillance Studies of Peste des Petits Ruminants (PPR) Virus in Sheep and Goats in South Asia: A Systematic Review and Meta-analysis

BackgroundPeste des Petits Ruminants (PPR), also known as the goat plague, is one of the WOAH-listed A, highly contagious and economically important viral transboundary animal diseases affecting small ruminants, and having a significant impact on the global livestock industry and international animal traffic. ObjectiveThe present study aimed to use a systematic approach to assess the pooled seroprevalence of PPRV in sheep and goats in South Asia, through a systematic review and meta-analysis of published data. MethodsA thorough search on various databases was performed to identify published research articles published between January 2000 and June 2025 reporting the seroprevalence of PPRV in small ruminants in South Asia. The articles were chosen on the basis of specific inclusion and exclusion criteria. Since the heterogeneity among the studies was significant, the pooled seroprevalence was estimated via a random effects meta-analysis model, using Stata (v19) and R software (v4.5.0). ResultsIn sheep and goats, the estimated pooled seroprevalence of PPR was 42.4% (95% CI: 35.0-49.9), whereas it was 41.8% (95% CI: 33.7-50.1) in goats and 44.5% (95% CI: 37.0- 52.0) in sheep. Subgroup analysis revealed that the pooled seroprevalence of PPRV in sheep and goat by country and vaccination status was greater in Nepal (57.0%, 95% CI: 8.4-97.7) and in vaccinated animals (57.5%, 95% CI: 47.9-66.9). ConclusionThis study highlights the need for coordinated actions, including vaccination, surveillance, and strict biosecurity, to control and eradicate the disease effectively. Moreover, authorities should adopt evidence-based strategies to support the global goal of eradicating PPR by 2030, as recommended by the WOAH.

microbiology↗

bioRxiv2025

WNK1 kinase activity is required for maintenance of podocyte structure

The filtration-function of glomeruli requires slit diaphragms formed by interdigitating podocyte foot processes, which are actin-based membrane protrusions. Dysregulation of mechanisms that maintain these membrane extensions lead to foot process effacement, proteinuria, and progression to chronic kidney disease. Building on our previous work that showed WNK1 kinase activity is necessary for the maintenance of normal biomechanical properties of glomeruli and podocyte foot process architecture, we tested the hypothesis that WNK1 kinase activity affects the structure of podocyte foot processes through modulation of actomyosin activity and focal adhesion complexes. Using a WNK1 kinase specific inhibitor, we determined by immunofluorescence microscopy of nascent focal adhesions, podocyte membrane spreading/extensions, and NMII paralog localization and extent of activation calculated from quantification of phosphorylated myosin, that all were sensitive to WNK1 kinase activity. Moreover, biochemical evidence of WNK1 kinase activity-dependent signalosomes supports a role for WNK1 in the maintenance of podocyte foot processes, and sarcomere-like structures (SLSs) that are induced in models of podocyte injury. Using primary and immortalized podocyte cell lines developed from control and Col4a3-/-Alport Syndrome model mice, we measured WNK1 kinase activity-dependent improvement in properties of injured podocytes in vitro. Physiological relevance of WNK1 kinase activity-dependent structural maintenance of podocyte foot processes was confirmed by significant acute proteinuria measured in response to WNK1 inhibition in vivo. Collectively, the results provide evidence that WNK1 kinase signalosome activity that includes formation of nascent focal adhesions and regulation of NMII localization and activity at membrane protrusions and extensions, are necessary for physiological maintenance of slit diaphragms. SignificanceTerminally differentiated podocytes are arborized cells with interdigitating foot processes that form the renal filtration barrier. Loss of foot process structural integrity causes progressive proteinuria, which can lead to irreversible renal injury, but the mechanisms that maintain foot process structure are incompletely understood. We report evidence that WNK1 kinase activity is required for maintenance of normal glomerular filtration in vivo, and this is mediated in part through WNK1 activity-dependent modulation of non-muscle myosin II activity, and formation of nascent focal adhesions that are necessary for lamellipodial extensions. Using glomeruli and podocyte cell lines developed from an Alport Syndrome podocyte injury model, we show that aspects of abnormal podocyte structure associated with chronic kidney disease can be suppressed through increased WNK1 activation.

cell biology↗

bioRxiv2025

Assessment of Meridic Gel Larval Diet and Meridic Adult Diet for Mass Rearing of Bactrocera dorsalis (Diptera: Tephritidae)

The oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae), is a widespread pest in Bangladesh. Sterile Insect Technique (SIT) offers a solution for effectively suppressing this fruit fly species. However, SIT involves mass rearing of fruit fly species in a laboratory where a standardized artificial rearing diet is crucial for ensuring uniform growth, development, and reproduction. In this study, we assessed efficacy of a new formulated gelbased meridic larval diet as well as protein and carbohydrate rich adult diets for the rearing of B. dorsalis in a laboratory condition. Proximate analysis was conducted for our formulated rearing diets to determine the content of moisture, protein, fat, carbohydrate, and ash. Several key biological parameters, including egg hatching rate, pupation rate, pupal weight, adult emergence, adult growth, sex ratio, and flight capacity, were assessed. Statistical analysis using Tukey box plots revealed a significant improvement in adult body parameters and an increase in longevity for our formulated diets. In addition, our study presents survival analysis using non-parametric Kaplan-Meier estimator and Weibull parametric model. This study shows that integrating our formulated diets into the mass rearing process of B. dorsalis in a laboratory could significantly improve the production of larger and healthier flies on a large scale.

zoology↗

bioRxiv2025

Mdm38/LETM1 couples ion homeostasis and proteostatic mechanisms in the inner mitochondrial membrane

The mitochondrial inner membrane is among the most protein-dense cellular membranes. Its functional integrity is maintained through a concerted action of several conserved mechanisms that are far from clear. Here, using the bakers yeast model, we functionally characterize Mdm38/LETM1, a disease-related protein implicated in mitochondrial translation and ion homeostasis, although the molecular basis of these connections remains elusive. Our findings reveal a novel role for Mdm38 in maintaining protein homeostasis within the inner membrane. Specifically, we demonstrate that Mdm38 is required for mitochondrial iron homeostasis and for signaling iron bioavailability from mitochondria to vacuoles. These processes are linked to the m- AAA quality control protease, whose unrestrained activity disrupts the assembly and stability of respiratory chain complexes in Mdm38-deficient cells. Our study highlights the central role of Mdm38 in mitochondrial biology and reveals how it couples proteostatic mechanisms to ion homeostasis across subcellular compartments.

biochemistry↗

bioRxiv2024

Scalable Fabrication of a Tough and Recyclable Spore-Bearing Biocomposite Thermoplastic Polyurethane

Thermoplastic polyurethanes (TPUs) are a class of versatile thermoplastic elastomers where most of their products lack a proper recycling strategy or have no end-of-life solutions. To pursue a sustainable end-of-life solution for TPU based products, self-disintegrating biocomposite TPUs have recently been developed by embedding spores of TPU-degrading bacteria into TPUs using melt extrusion. Herein, we improve upon spore-bearing biocomposites and demonstrate industrially-relevant manufacturing conditions for the fabrication of biocomposite TPUs. Spore production was modified to reduce the innate brown color of the resulting materials and, effectively minimize the coloration of biocomposite TPUs. Reduction of FeSO4 in a sporulation media generated white spores without compromising spore productivity, viability, morphology or heat-shock tolerance. Biocomposite TPUs containing white spores displayed a 45% increase in toughness compared to TPUs without spores, while retaining [~]90% spore viability post processing. Furthermore, biocomposite TPU fabrication was demonstrated using a scalable continuous extruder followed by injection molding. Biocomposite TPUs generated by these industry-relevant processes exhibited comparable toughness improvement and spore viability to biocomposite TPU prepared using a lab scale microcompounder, while enhancing productivity by 30-fold. Finally, spore addition improved biocomposite TPUs recyclability, enabling 80% toughness retention after 5 rounds of iterative melt processing. Additionally, no negative effect on the lifespan of the generated TPUs was observed over a duration of 1 year of storage. Overall, this study confirmed that spore-bearing biocomposite TPUs are promising for practical applications, offering an accessible method to enhance toughness and sustainability of commercial TPUs through the incorporation of spore-based living fillers.

bioengineering↗

bioRxiv2024

Structural enzymological studies of the long chain fatty acyl-CoA synthetase FadD5 from the mce1 operon of Mycobacterium tuberculosis

The cell wall of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is rich in complex lipids. During intracellular stage, Mtb depends on lipids for its survival. Mammalian cell-entry (Mce) 1 complex encoded by the mce1 operon is a mycolic/fatty acid importer. mce1 operon also encodes a putative fatty acyl-CoA synthetase (FadD5; Rv0166), potentially responsible for the activation of fatty acids imported through the Mce1 complex by conjugating them to Coenzyme A. Here we report that FadD5 is associated to membrane although it can be purified as a soluble dimeric protein. ATP and CoA binding influence FadD5s stability and conformation respectively. Enzymatic studies with fatty acids of varying chain lengths show that FadD5 prefers long chain fatty acids as substrates. X-ray crystallographic studies on FadD5 and its variant reveal that the C-terminal domain ([~]100 residues) is cleaved off during crystallization. Noteworthy, deletion of this domain renders FadD5 completely inactive. SAXS studies, however, confirm the presence of full length FadD5 as a dimer in solution. Further structural analysis and comparisons with homologs provide insights on the possible mode of membrane association and fatty acyl tail binding.

biochemistry↗

bioRxiv2024

Mycolic acid and cholesterol induced transcriptomic adaptations in wild type and Mce complex ATPase subunit deleted strain of M. tuberculosis H37Rv

During infection and latency, Mycobacterium tuberculosis (Mtb) primarily relies on lipids as its main energy source. The Mtb mammalian cell entry (Mce) complexes function as lipid transporters with Mkl as the ATPase subunit for substrate translocation. Cholesterol and mycolic acid are essential to the infectiousness and pathogenicity of Mtb. Here, we have investigated the transcriptomic responses of wild type and{Delta} mkl strains of Mtb to cholesterol and mycolic acid through RNAseq analysis. The number of differentially expressed genes was always higher when grown on cholesterol than on mycolic acid. In most cases,{Delta} mkl showed the opposite gene expression pattern compared to the wild type. Among the four mce operons, significant changes in expression patterns were observed mainly in the genes of mce3 and mce4 operons. The upregulation of mce3 operon and the downregulation of mce4 operon in the presence of mycolic acid and cholesterol is intriguing. The transcriptome profile of genes involved in mycolic acid synthesis did not show significant change to either mycolic acid or cholesterol. However, interestingly, both mycolic acid and cholesterol induce upregulation of methyl citrate cycle and dormancy related genes indicating their significance during Mtb persistence and provides insights on Mtbs adaptive strategies under stress through transcriptional remodelling.

biochemistry↗

bioRxiv2024

Beyond the Sin3/HDAC Complex: FAM60A emerges as a regulator of RNA Splicing

FAM60A, traditionally linked to chromatin remodeling within the Sin3/HDAC complex, has emerged as a critical regulator in RNA splicing. Employing an integrative approach that combines immunological assays, CRISPR/Cas9 technology, comprehensive genomics, proteomics, and advanced cross-linking mass spectrometry, complemented by sophisticated 3D molecular modeling, our study challenges and extends the existing understanding of FAM60As functional dynamics. Contravening previous perceptions, our findings elucidate that FAM60A does not interact directly with SIN3A, rather establishes direct interactions with SAP30 and HDAC1, redefining its relationship with the Sin3/HDAC complex. These interactions, deciphered through detailed 3D structural analysis supported by cross-linking constraints, signify a complex architectural role of FAM60A within chromatin remodeling processes. Moreover, our research unveils FAM60As pivotal role in RNA processing, particularly in splicing regulation. Through extensive molecular interactions with a diverse array of mRNA-binding proteins and principal spliceosome components, FAM60A emerges as a key regulator of RNA splicing. This expanded role delineates its influence on gene expression regulation, spotlighting its capacity to modulate critical cellular processes. In sum, this study unveils FAM60As key role in gene regulation and RNA splicing, and suggests new paths for cellular and therapeutic research.

molecular biology↗

bioRxiv2023

Biocomposite Thermoplastic Polyurethanes Containing Evolved Bacterial Spores as Living Fillers to Facilitate Polymer Disintegration

The field of engineered living materials (ELMs) seeks to pair living organisms with synthetic materials to generate biocomposite materials with augmented function since living systems can provide highly-programmable and complex behavior. ELMs have typically been fabricated using techniques in benign aqueous environments, limiting their application. In this work, biocomposite fabrication was demonstrated in which spores from polymer-degrading bacteria were incorporated into a thermoplastic polyurethane (TPU) using high-temperature melt processing. Bacteria were engineered using adaptive laboratory evolution to improve their heat tolerance to ensure nearly complete cell survivability during manufacturing at 135 {degrees}C. Furthermore, the overall tensile properties of spore-filled TPUs were substantially improved, resulting in a significant improvement in toughness. The biocomposites facilitated disintegration in compost in the absence of a microbe-rich environment. Finally, spores retained a programmed function, expressing green fluorescent protein. This research provides a scalable method to fabricate advanced biocomposite materials in industrially-compatible processes.

bioengineering↗

bioRxiv2023

The CB1 Negative Allosteric Modulator PSNCBAM-1 Reduces Ethanol Self-Administration via a Nonspecific Hypophagic Effect

Alcohol use disorder (AUD) affects more than 15 million people in the United States. Current pharmacotherapeutic treatments for AUD are only modestly effective, necessitating the identification of new targets for medications development. The cannabinoid receptor type 1 (CB1) has been a target of interest for the development of medications for substance use disorders and other compulsive disorders. However, CB1 antagonists/inverse agonists (e.g., rimonabant) have severe side effects that limit their clinical utility, including anxiety, depression, and suicide. Recent development of CB1 negative allosteric modulators (NAMs), including PSNCBAM-1, may provide an alternative mechanism of attenuating CB1 signaling with reduced side effects. PSNCBAM-1 has not yet been evaluated for effects in models of AUD. In this study, we investigated the effects of the CB1 NAM, PSNCBAM-1, in rodent models of AUD using adult male mice. PSNCBAM-1 dose-dependently attenuated oral ethanol self-administration (8% w/v ethanol in water), significantly reducing ethanol rewards at a dose of 30 mg/kg, but not at 10 or 18 mg/kg. PSNCBAM-1 also dose-dependently attenuated palatable food self-administration (diluted vanilla Ensure), significantly reducing food rewards at 18 and 30 mg/kg PSNCBAM-1. PSNCBAM-1 did not affect conditioned place preference for 2 g/kg ethanol. These results suggest PSNCBAM-1 reduces ethanol-taking behavior via a nonspecific hypophagic effect and does not reduce the rewarding effects of ethanol.

pharmacology and toxicology↗

bioRxiv2023

Identification of Natural Antiviral Drug Candidates Against Tilapia Lake Virus: Computational Drug Design Approaches

Tilapia Lake Virus (TiLV) is a disease that affects tilapia fish, causing a high rate of sudden death at any stage of their growth. Unfortunately, there are currently no effective antiviral drugs or vaccines to control the progression of this disease. Researchers have discovered that the CRM1 protein plays a critical function in the development and spreading of animal viruses. By inhibiting CRM1, the viruss spread in commercial fish farms can be suppressed. With this in mind, this study intended to identify potential antiviral drugs from two different tropical mangrove plants from tropical regions: Heritiera fomes and Ceriops candolleana. To identify promising compounds that target the CRM1 protein, a computer-aided drug discovery approach is employed containing molecular docking, ADME (absorption, distribution, metabolism and excretion) analysis, toxicity assessment as well as molecular dynamics (MD) simulation. To estimate binding affinities of all phytochemicals, molecular docking is used and the top three candidate compounds with the highest docking scores were selected, which are CID107876 (-8.3), CID12795736 (-8.2), and CID12303662 (-7.9). We also evaluated the ADME and toxicity properties of these compounds. Finally, molecular dynamics simulation was conducted to analyze the stability of the protein-ligand complex structures and confirm the suitability of these compounds. The computational study demonstrated that the phytochemicals found in H. fomes and C. candolleana could potentially serve as important inhibitors of TiLV, offering practical utility. However, further in vivo investigations are necessary to investigate the effectiveness of these compounds as antiviral drugs against the virus TiLV.

pharmacology and toxicology↗

bioRxiv2023

Identification of Therapeutic Leads from Ficus hispida Fruit Phytochemicals against Prostate Cancer Using Pharmacoinformatic and Molecular Dynamics Simulation Approach

Prostate cancer is one of the leading causes of death and the most common cancer type in men. In this study, potential leads from the phytochemicals of Ficus hispida fruit were screened using in silico tools against androgen receptor (AR), a known target for prostate cancer. PASS online and ADMET tools were used to screen specific phytochemicals that are relevant to prostate cancer treatment and have drug-like properties. Of 13, a total of 10 phytochemicals passed PASS online and ADMET screening. Next, a total of three phytochemicals, including nodakenetin (CID: 26305), isowigtheone hydrate (CID: 66728267), and 7-hydroxycoumarin (CID: 5281426) were selected based on their docking scores (-9.946 to -7.653 kcal/mol) and relevance to selective bioactivity. The MD simulation further confirmed the binding stability of these three phytochemicals with their target AR protein and determined that the main amino acid residues mainly responsible for this stability including RMSD, RMSF, and post simulation binding free energies. These findings suggest that these three phytochemicals of Ficus hispida fruit can further be developed as prospective therapeutics against prostate cancer.

bioinformatics↗