bioRxiv Science⌕ Search

Biology subjects

Fatema, K.

Publications and source records attributed to Fatema, K..

7 recordsLinked to original sources
bioRxiv2026

Integrated in silico identification of fungal-derived dual-target inhibitors for anti-schistosomal drug discovery

Praziquantel, which has limited efficacy against young parasites and reduces susceptibility, is the principal therapy for schistosomiasis, a neglected tropical illness. This work identified fungal-derived compounds with potential dual inhibitory action against Schistosoma mansoni DHODH and cathepsin B1 using an integrated computational method. From 1,831 fungal metabolites, 120 were selected for molecular docking after structure standardisation, drug-likeness evaluation, ADMET, and toxicity screening. Ganoderlactone B (CID_122184973) and Spiroapplanatumine F (CID_132962217) strongly bound to DHODH and CB1, with docking affinities of -10.6 and -10.0 kcal/mol and -9.0 and -8.9, respectively. Docking validation showed good discrimination between active compounds and decoys with area-under-the-curve values of 0.98 for DHODH and 0.96 for CB1. The protein-ligand interaction study showed hydrogen bonding, hydrophobic interactions, and van der Waals contacts at the binding sites. In 100 ns molecular dynamics simulations, protein complexes exhibited modest backbone deviations and maintained compactness, although CID_132962217 showed sustained binding and a constrained conformation. MM-PBSA analysis identified CID_122184973 as the best common ligand for both targets. At the B3LYP/6-31G level, density functional theory calculations showed that CID_139584993 had the lowest HOMO-LUMO energy gap and hardness values of 3.552 and 1.776 eV, respectively, and the highest softness value of 0.282 eV-1, indicating greater electronic reactivity. Electrostatic potential mapping and QSAR predictions supported their interaction and antiparasitic potential. Overall, CID_122184973 and CID_132962217 are promising fungal scaffolds for dual-target anti-schistosomal drug development. Experimental enzyme inhibition, parasite viability, toxicity, and in vivo research are needed to confirm computational findings.

bioinformatics↗
bioRxiv2026

SWI/SNF Alterations Define a Chromatin-Dependent Subtype of Urothelial Carcinoma

PurposeSWI/SNF (BAF) chromatin remodeling complex alterations are common in urothelial carcinoma, yet no biomarker-directed therapeutic strategies have been established for this population. We investigated whether BAF alterations delineate a biologically distinct, therapeutically actionable urothelial carcinoma subtype. Experimental DesignWe performed integrative genomic and transcriptomic analyses of 792 urothelial carcinoma tumors from the Oncology Research Information Exchange Network (ORIEN) and validated findings in the TCGA-BLCA cohort. Mechanistic studies incorporated RNA sequencing and ATAC-seq following histone deacetylase (HDAC) inhibition. Functional dependencies were assessed using patient-derived xenograft organoids and cell line models. Clinical relevance was explored in a biomarker-enriched investigator-initiated trial. ResultsApproximately half of urothelial carcinoma tumors exhibited BAF alterations, defining a previously unrecognized chromatin-altered molecular subtype characterized by activation of proliferative programs, loss of lineage identity, and altered metabolic signaling. This subtype was enriched for transcriptomic programs associated with HDAC inhibitor sensitivity and depleted of HDAC inhibitor resistance signatures. Mechanistically, HDAC inhibition induced widespread chromatin remodeling with reduced accessibility at AP-1 and TEAD-associated regions, and downregulation of E2F- and MYC-driven transcriptional networks. Functional studies confirmed enhanced HDAC inhibition sensitivity in ARID1A-mutated cell lines and a patient-derived organoid model. Early clinical observations demonstrated a durable responder treated with HDAC inhibitors and immunotherapy. ConclusionsBAF alterations define a chromatin-dependent tumor state in urothelial carcinoma that is selectively vulnerable to HDAC inhibition. Integrating genomic, epigenomic, functional, and early clinical evidence, these findings provide a rationale for biomarker-enriched clinical trials and HDAC inhibitor-based combination strategies in urothelial carcinoma.

cancer biology↗
bioRxiv2026

Defining biologically directed therapy target signatures in urothelial carcinoma: A transcriptomic framework for precision therapy

IntroductionNectin-4 targeting antibody-drug conjugate (ADC) enfortumab vedotin (EV), in combination with pembrolizumab, is the first-line treatment for patients with locally advanced or metastatic urothelial carcinoma (UC). Optimal treatment strategies for patients who are non-responders or progress on EV with pembrolizumab remain an unmet clinical need. We sought to characterize ADC and immunotherapy (IO)-associated target expression profiles to identify candidate therapeutic vulnerabilities beyond EV. MethodsWe conducted a literature review to identify ADC and IO targets with approved or investigational relevance in UC. Unsupervised hierarchical clustering was used to identify clusters of target gene expression in RNA-seq data. Transcriptomic clustering analyses were performed in 434 patients from The Cancer Genome Atlas Bladder Urothelial Carcinoma cohort (TCGA-BLCA) and validated in an independent cohort of 478 patients from the Oncology Research Information Exchange Network (ORIEN) consortium. Proteomic interrogation of these targets was performed using mass spectrometry data from additional cohort of 116 patients. Differential gene expression analyses evaluated associations between target expression patterns, histologic variants, and consensus molecular subtypes of muscle-invasive bladder cancer (CMIBC). ResultsWe identified 13 ADC and 10 IO-associated targets with translational relevance in UC. Transcriptomic analyses revealed three reproducible clusters of overexpressed target genes across independent cohorts: 1) a luminal/epithelial-associated cluster enriched for VTCN1, SLITRK6, FGFR3, NECTIN4, TACSTD2, ERBB2, and ERBB3; 2) an immune target predominant cluster enriched for BTLA, LAG3, PDCD1, TIGIT, CTLA4, TNFRSF9, TNFRSF18, TNFRSF4; and 3) a basal/neuroendocrine-associated cluster characterized by CD274, F3, NT5E, EGFR, MET and DLL3. Similar clusters were largely conserved at the proteomic level. Adenocarcinomas overexpressed ERBB3 compared to neuroendocrine and squamous cell carcinomas. Pure squamous cell carcinomas overexpressed TACSTD2 compared to adenocarcinomas. In CMIBC subtypes, basal/squamous tumors expressed higher levels of CD274, EGFR, F3, LAG3, NT5E, and TNFRSF18, whereas luminal tumors demonstrated higher ERBB2 and ERBB3 expression. Neuroendocrine-like tumors showed higher DLL3 expression compared to all other subtypes. Tumors with low expression of NECTIN4, TACSTD2, and FGFR3 were enriched for alternative targets including DLL3, CD274, and CD276. Our findings provide a framework for hypothesis-driven therapeutic prioritization in advanced UC. Conclusions: UC is characterized by reproducible, biologically distinct patterns of ADC and IO target expressions. The degree of expression of NECTIN4 was positively associated with TACSTD2, FGFR3 and inversely associated with DLL3, CD276, and CD274, supporting alternative biologically informed treatment strategies besides EV . Histologic variants and molecular subtypes of UC also display distinct patterns of target expression. This study provides the first integrated transcriptomic framework linking ADC and IO target co-expression patterns for hypothesis-driven therapeutic prioritization. These findings provide a basis for rational ADC and immunotherapy development in advanced UC and support prospective proteomic validation in treatment stratified cohorts. Statement of Translational RelevanceEnfortumab vedotin plus pembrolizumab has redefined first-line therapy for advanced urothelial carcinoma, yet treatment selection following resistance or progression remains undefined. In this study, we integrate transcriptomic and proteomic analyses across independent cohorts to define reproducible patterns of antibody-drug conjugate (ADC) and immunotherapy target co-expression in urothelial carcinoma. We identify biologically distinct target-expression patterns that are associated with histologic and molecular subtypes and demonstrate coordinated and, in some cases, mutually exclusive relationships among therapeutically actionable targets. These findings have direct translational implications. First, they provide biologic rationale for rational sequencing and combination strategies based on co-expressed targets in NECTIN4-enriched tumors. Second, they identify alternative therapeutic vulnerabilities, including DLL3- and CD274-associated pathways, in tumors with low NECTIN4 expression, a population potentially enriched for resistance to EV-based therapy. Finally, this framework establishes a foundation for biomarker-driven clinical trials in urothelial carcinoma and supports the development of precision therapeutic approaches beyond current standards.

cancer biology↗
bioRxiv2024

Phytochemical and Therapeutic Evaluation of Ficus nervosa Leaves: Impact on Oxidative Stress, Analgesic, Diarrhea, and Blood Clotting in a Mice Model

BackgroundFicus nervosa (FN) leaves have been traditionally used in ethnomedicine for the treatment of various ailments, this study aimed to investigate the cold methanol extract of FN for its antioxidant, analgesic, antidiarrheal, and thrombolytic properties, along with preliminary phytochemical screening to identify key bioactive compounds and acute toxicity test to assess the safety profile of the extract. MethodsIn this study, we conducted an initial investigation to identify the major phytochemical groups present in the leaves of Ficus nervosa. Using conventional phytochemical screening methods on cold methanol extracts, we consistently identified phenols and flavonoids as the predominant bioactive compounds. Following this phytochemical characterization, we assessed the biological activities of the extracts across multiple models. The antioxidant capacity and free radical-scavenging ability of the leaves extracts were evaluated using the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Analgesic efficacy was assessed through acetic acid-induced writhing and electrically induced heat nociception tests. Antidiarrheal effects were examined using castor oil-induced diarrhea and an enteropooling assay in mice. To determine thrombolytic activity, we conducted a human blood clot lysis assay, while preclinical toxicity testing was conducted to evaluate the safety profile of the extracts. Statistical analysis was performed using one-way ANOVA with Duncans Multiple Range Test (DMRT) to validate the significance of the results. ResultsThe study of Antioxidant Potential, the ESFs (ethyl soluble fraction) antioxidant capacity, measured at 409.91 {+/-} 0.59 mg of ascorbic acid equivalent (AAE)/g in the phosphomolybdenum assay, signifies a strong free radical scavenging activity. This level of antioxidant action, alongside a potent free radical neutralizing concentration (IC of 9.99 {+/-} 0.41 g/mL), suggests that the ESF could effectively counteract oxidative stress. Analgesic activity at 500 mg/kg, FN extract produced a 68.05% suppression of writhing in mice, which was statistically significant (p<0.001) compared to standard morphines (74.05%) inhibition. The extract also significantly prolonged reaction latency to thermal-induced pain in hotplate model. The antidiarrheal activity showed 52.09% and 59.0% suppression of defecation, compared to standard loperamides 73.1%, with statistically significant p-values (p<0.04 and p<0.01). These effects, combined with the notable decrease in intestinal fluid accumulation and defecation frequency in enteropooling assays, indicate that FN extract might interact with intestinal motility or fluid secretion pathways, providing antidiarrheal benefits. Additionally, the chloroform-soluble fraction of FN exhibited moderate thrombolytic activity, achieving 39.79% clot lysis compared to streptokinase (69.52%). Although this thrombolytic potential is moderate, it indicates that the fraction contains compounds with some fibrinolytic properties, which could be useful as adjunctive agents in preventing thrombosis. ConclusionOverall, the cold methanol extract of FN leaves demonstrates the therapeutic potential in preclinical settings. Future research is warranted to isolate the specific bioactive compounds and explain their mechanisms of action to further support the development of new treatments and contributing to modern medicinal practices based on this plant leaves.

plant biology↗
bioRxiv2024

A VLP vaccine platform comprising the core protein of hepatitis B virus with N-terminal antigen capture

Nanoparticle presentation systems offer the potential to develop new vaccines rapidly in response to emerging diseases, a public health need that has become increasingly evident in the wake of the COVID-19 pandemic. Previously, we reported a nanoparticle scaffold system termed VelcroVax. This was constructed by insertion of a high affinity SUMO binding protein (Affimer), able to recognise a SUMO peptide tag, into the major immunodominant region of VLPs assembled from a tandem (fused dimer) form of hepatitis B virus (HBV) core protein (HBc). Here we describe a modified form of VelcroVax, comprising monomeric HBc with the Affimer inserted at the N-terminus (termed N-VelcroVax). In contrast to the tandem form of VelcroVax, N-VelcroVax VLPs were expressed well in E. coli. The VLPs effectively bound SUMO-tagged Junin virus glycoprotein, gp1 as assessed by structural and serological analyses. Cryo-EM characterisation of N-VelcroVax complexed with a SUMO-Junin gp1 showed continuous density attributable to the fused Affimer, in addition to evidence of target antigen capture. Collectively, these data suggest that N-VelcroVax has potential as a versatile next generation vaccine scaffold.

molecular biology↗
bioRxiv2023

Enhancing Rice Growth and Yield with Weed Endophytic Bacteria Alcaligenes faecalis and Metabacillus indicus Under Reduced Chemical Fertilization

Endophytic bacteria, recognized as eco-friendly biofertilizers, have demonstrated the potential to enhance crop growth and yield. While the plant growth-promoting effects of endophytic bacteria have been extensively studied, the impact of weed endophytes remains less explored. In this study, we aimed to isolate endophytic bacteria from native weeds and assess their plant growth-promoting abilities in rice under varying chemical fertilization. The evaluation encompassed measurements of mineral phosphate and potash solubilization, as well as indole-3-acetic acid (IAA) production activity by the selected isolates. Two promising strains, tentatively identified as Alcaligenes faecalis (BTCP01) from Eleusine indica (Goose grass) and Metabacillus indicus (BTDR03) from Cynodon dactylon (Bermuda grass) based on 16S rRNA gene phylogeny, exhibited noteworthy phosphate and potassium solubilization activity, respectively. BTCP01 demonstrated superior phosphate solubilizing activity, while BTDR03 exhibited the highest potassium (K) solubilizing activity. Both isolates synthesized IAA in the presence of L-tryptophan, with the detection of nifH and ipdC genes in their genomes. Application of isolates BTCP01 and BTDR03 through root dipping and spraying at the flowering stage significantly enhanced the agronomic performance of rice variety BRRI dhan29. Notably, combining both strains with 50% of recommended N, P, and K fertilizer doses led to a substantial increase in rice grain yields compared to control plants receiving 100% of recommended doses. Taken together, our results indicate that weed endophytic bacterial strains hold promise as biofertilizers, potentially reducing the dependency on chemical fertilizers by up to 50%, thereby fostering sustainable rice production.

microbiology↗