Biology subjects

Sahu, V. K.

Publications and source records attributed to Sahu, V. K..

5 recordsLinked to original sources

bioRxiv2025

Integrative Transcriptomics and Phytochemical Screening Reveal Pratenol B, Eriodictyol, Losbanine, and Isookanin, as Potential EGFR and HRAS Inhibitors in Indian Oral Squamous Cell Carcinoma Patients

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, with India contributing nearly one-third of the global cases. Management of OSCC remains difficult due to increasing risk factors, limited therapeutic options, severe side effects, and rising drug resistance. Therefore, novel and safer treatment strategies are urgently needed. This study explores the potential of phytochemicals as targeted inhibitors of key dysregulated biomarkers in Indian OSCC patients. RNA sequencing and pathway analysis revealed significant alterations in the MAPK signaling pathway, highlighting EGFR and HRAS as crucial therapeutic targets. Given the limited clinical success of existing EGFR-targeted therapies and the scarcity of HRAS inhibitors, a natural product-based approach was adopted. Molecular docking of 17,000 phytochemicals identified Pratenol B, Eriodictyol, Losbanine, and Isookanin as promising inhibitors, with Pratenol B showing dual inhibition of EGFR and HRAS. These compounds exhibited strong binding affinities, favorable pharmacokinetic profiles, high bioavailability, and low toxicity. Molecular dynamics simulations confirmed the stability of Pratenol B with both target proteins, surpassing reference inhibitors. Utilizing vast medicinal plant diversity presents a cost-effective and low-toxicity avenue for OSCC therapy. Further in vitro, in vivo, and clinical studies are warranted to validate these phytochemicals as potential therapeutics.

cancer biology↗

bioRxiv2025

SieveAI: Development of an Automated extensible and customisable drug discovery pipeline and its validation

Systematic Interaction Evaluation and Virtual Enhancement Analysis Interface (SieveAI) is an automated drug discovery pipeline developed to enhance the efficiency of virtual screening and computer-aided drug discovery processes. The molecular docking workflow encompasses acquiring, modeling, and pre-processing of molecular structure files, conducting docking with various algorithms, and subsequent analysis and interpretation of the outcomes by visualising or tabulating the results. While several open-source software tools are available to assist these operations at different steps of molecular docking, they often necessitate manual user intervention at every stage. To streamline and automate this extensive manual process and develop a comprehensive solution, we have developed an innovative, fully extensible, molecular docking pipeline SieveAI ((C)L-129927/2023). The same has been demonstrated in this manuscript. SieveAI works with a range of open-source libraries, packages, and programs to facilitate automated drug discovery using established programs and software. The package is accessible at https://miRNA.in/SieveAI.

bioinformatics↗

bioRxiv2024

Unveiling theranostic potential: Insights into cell-free microRNA-protein interactions

MicroRNAs (miRNAs) belong to a short endogenous class of non-coding RNAs which have been well studied for their crucial role in regulating cellular homeostasis. Their role in modulation of diverse biological pathways by intracellular or extracellular communication and interaction with DNA, RNA or protein, projects them or their targets as promising biomarkers and therapeutic agents. However, studying specific interactions in the extracellular or cell-free environment for drug discovery or biomarker establishment is resource-intensive. In this study, we derive a computational approach based on available experimental data to decipher patterns in miRNA-protein interactions in the cell-free milieu. We characterized the miRNA-protein interactome (miRPin, https://www.mirna.in/miRPin) and identified consensus sequences governing these interactions. The study establishes the role of multiple miRNAs and protein interactions present in cell-free environments leading to pathological conditions, viz., role of proteins like METTL3 and AGO2 etc. and miRNAs like hsa-miR-484 and hsa-miR-30 families, hsa-mir-126-5p etc. in association with multiple miRNAs in different cancer types, cardiovascular diseases, and neurological disorders. The findings outlined in the study may facilitate new avenues of therapeutic discovery leading to the understanding of cellular mechanisms underlying therapy relapse and drug resistance. By addressing these interactions in an extracellular environment may further gain insight into regulating disease initiation and progression, overcoming challenges related to drug efficacy and drug delivery in the presence of bilayer membranes with drug efflux pumps.

bioinformatics↗

bioRxiv2024

A Dual intervention of Triiodothyronine and Baicalein bi-directionally upregulates Klotho with attenuation of chronic kidney disease and its complications in aged BALB/c mice

Chronic kidney disease (CKD) is a global health challenge marked by progressive renal decline and increased mortality. The interplay between CKD and hypothyroidism, particularly nonthyroidal low-triiodothyronine (T3) syndrome, exacerbates disease progression, driven by HPT axis dysfunction and reduced Klotho levels due to Wnt-{beta}-catenin pathway activation. This study explored Klotho as a link between CKD and hypothyroidism using an adenine-induced CKD aged mouse model. Exogenous T3 and baicalein (BAI), targeting the Wnt pathway, were used to upregulate Klotho expression. Combined T3 and BAI treatment significantly increased Klotho levels, surpassing individual effects, and suppressed key signaling molecules (TGF, NF{kappa}B, GSK3), mitigating renal fibrosis and CKD complications, including cardiovascular disorders and dyslipidemia. This bidirectional approach, enhancing Klotho via T3 and sustained Wnt pathway inhibition, offers a novel and effective strategy for CKD management, particularly in elderly patients with hypothyroidism.

biochemistry↗

bioRxiv2023

miRVim: Three-dimensional miRNA Structure Data Server

MicroRNAs (miRNAs), a distinct category of non-coding RNAs, exert multifaceted regulatory functions in a variety of organisms, including humans, animals, and plants. The inventory of identified miRNAs stands at approximately 60,000 among all species and 1,926 in Homo sapiens manifests miRNA expression. Their theranostic role has been explored by researchers over the last few decades, positioning them as prominent therapeutic targets as our understanding of RNA targeting advances. However, the limited availability of experimentally determined miRNA structures has constrained drug discovery efforts relying on virtual screening or computational methods, including machine learning. To address this limitation, miRVim has been developed, providing a repository of human miRNA structures derived from both two-dimensional (MXFold2, CentroidFold, and RNAFold) and three-dimensional (RNAComposer and 3dRNA) structure prediction algorithms, in addition to experimentally available structures from the RCSB PDB repository. This data server aims to facilitate computational data analysis for drug discovery, opening new avenues for advancing technologies such as machine learning-based predictions in the field. The publicly accessible structures provided by miRVim, available at https://mirna.in/miRVim, offer a valuable resource for the research community, advancing the field of miRNA-related computational analysis and drug discovery.

bioinformatics↗