Biology subjects

Umrao, S.

Publications and source records attributed to Umrao, S..

3 recordsLinked to original sources

bioRxiv2026

APIPred Web 1.0: A Web Platform to Predict Potential Aptamer Sequences for Protein targets

Aptamers are short single-stranded nucleic acids that bind protein targets with high specificity and are increasingly used in diagnostics and therapeutics, yet experimental discovery remains slow and variable in success. This creates a demand for computational systems that not only score candidate binders but also generate experimentally usable libraries under biologically meaningful constraints. Here, we present APIPred Web 1.0, a unified web platform that integrates constraint-aware aptamer library generation, machine learning- based aptamer- protein interaction prediction, and DNA secondary-structure analysis within a user-facing workflow. Users submit a target protein aminoacid sequence and define an aptamer template in a PREFIX - [VARIABLE] - SUFFIX format with real-time validation of key biological constraints (GC content and homopolymer limits). On the backend, sequences are converted into model- compatible features via optimized k-mer encodings (aptamer) and pseudo amino acid composition (PAAC) descriptors (protein), followed by inference with a trained XGBoost predictor. APIPred Web 1.0 improves the computational efficiency by applying precomputed protein features, vectorized batch processing (hundreds of sequences per batch), optimized XGBoost DMatrix inference, and a bounded heap that retains only the top 25 candidates during generation. The platform then computes minimum free energy (MFE) structures using ViennaRNA with parallel folding and returns ranked list of the top candidates with log-transformed interaction scores, complete sequences (variable region highlighted), dot-bracket structures, MFE values, and interactive 2D visualizations via persistent result links. In a demonstration study targeting CD64 protein, the platform produced 25 putative binders from a custom 40- nucleotide library and enabled selection of structurally diverse candidates for experimental testing. Flow cytometry showed specific binding to CD64-expressing THP-1 cells with minimal signal in Ramos control cells. Collectively, APIPred Web 1.0 offers a reproducible, structure-informed, and computationally efficient pipeline for rapid generation of aptamer candidates against target proteins for downstream experimental validation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=50 SRC="FIGDIR/small/697194v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@1c1ca4dorg.highwire.dtl.DTLVardef@1c8b23dorg.highwire.dtl.DTLVardef@12dfe2dorg.highwire.dtl.DTLVardef@8a7c8f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

Broad-Spectrum HIV-1 Detection and Neutralization via Multivalent Designer DNA Nanostructures

Early and accurate detection of HIV-1 remains a critical unmet need, particularly during the acute phase of infection when viral loads are low and transmission risk is highest. Here, we report a modular diagnostic and antiviral platform based on designer DNA nanostructures engineered for high-affinity recognition of the HIV-1 envelope glycoprotein (GP120). A custom DNA aptamer, termed HINT, was developed to bind GP120 across major HIV-1 subtypes (Groups M and P; subtypes A and B) with nanomolar affinity. To amplify binding strength, HINT aptamers were spatially patterned onto a net-shaped DNA nanostructure (DNA-NetHINT) that geometrically matches the trimeric GP120 spikes on the viral surface. Using multivalent interactions, the nanostructure enabled up to 104-fold improvement in binding affinity (sub-picomolar KD), confirmed by surface plasmon resonance. Integration of DNA-NetHINT into a paper-based lateral flow assay produced a low-cost, saliva-compatible self-testing device capable of detecting intact HIV-1 virions at concentrations as low as 328 viral copies per test, outperforming commercial fourth-generation rapid diagnostic tests. In addition to its diagnostic capabilities, the DNA-NetHINT construct exhibited potent antiviral activity, reducing pseudovirus infection with an EC50 of [~]1.8 nM, nearly 1,000-fold more effective than free aptamers. This work demonstrates a dual-function DNA nanotechnology platform that enables both ultrasensitive HIV-1 detection and entry inhibition. The approach is broadly applicable to other enveloped viruses and represents a promising step toward next-generation molecular theranostics for infectious disease management.

bioengineering↗

bioRxiv2025

Hybrid peptide DNA nanomaterials enable potent and broad-spectrum virus neutralization

The continued emergence of antigenic drift and drug-resistant viral strains highlights the need for antiviral strategies that deliver robust efficacy, broad subtype coverage, and minimal off-target toxicity. We demonstrate a potent and broad-spectrum strategy that employs hybrid biomaterials of Urumin (a host defense peptide) and a honeycomb (HC) DNA origami through spatially organized multivalent presentation for enhanced antiviral efficacy. Molecular dynamics simulations reveal that Urumin penetrates and destabilizes the hemagglutinin (HA) trimer core, disrupting influenza A viral (IAV) entry. Arranging Urumin in trimeric clusters on the HC enables potent multivalent binding to trimeric HAs on IAV, enhancing antiviral efficacy at nanomolar concentrations, [~]1,000-fold more effective than free Urumin. In vitro assays confirm HC-Urumin outperforms free Urumin in blocking viral entry and preserving cell viability in more IAV subtypes. In vivo studies show that compared to free Urumin, HC-Urumin treatment reduces disease severity, preserves physiological behavior, and decreases mortality in infected mice, while maintaining virus-specific adaptive immune responses without altering humoral immunity. Our study offers an advanced and effective materials platform and strategy for broad-spectrum, low-dose intervention against human and animal IAVs, which can be adapted to combat other viruses by patterning corresponding host defense peptides on custom designed DNA nanostructures.

bioengineering↗