Biology subjects

Pandey, R. K.

Publications and source records attributed to Pandey, R. K..

7 recordsLinked to original sources

bioRxiv2026

Computational Designing of a Multi-Epitope Vaccine Against Streptococcus pyogenes

Group A Streptococcus (GAS), or Streptococcus pyogenes is almost exclusive and greatly adapted human pathogen. It causes a wide array of clinical symptoms, ranging from minor infections of the skin and soft tissues to pharyngitis, meningitis, pneumonia, bacteraemia, cellulitis, puerperal sepsis, and necrotising fasciitis. The risk of S. pyogenes infection is known to be influenced by several host characteristics, including age, underlying diseases like diabetes, varicella, or skin lesions, both chronic and acute, and certain risk behaviours such as use of drugs. Household size and overcrowding are two environmental factors that significantly affect the transmission of S. pyogenes. The majority of cases occur spontaneously in the community, and preventative opportunities are still limited. A large portion of GAS-related mortality is found in low-income areas and communities. Based on aforementioned public health risk, the creation of effective therapeutic vaccines would be an excellent addition to current control measures. The purpose of this work is to address the need for new instruments to aid in the elimination of S. pyogenes infections. The discovery of high antigenic regions in several highly conserved proteins brings us one step closer to developing peptide vaccines capable of influencing the different phases of S. pyogenes infection, providing more effective defence and greater serotype coverage. This study used various techniques of immunoinformatics to design an effective multi-epitope vaccine that produced neutralising antibodies against multiple strains of S. pyogenes.

bioinformatics↗

bioRxiv2026

An Integrated Computational Approach to Predict and Characterize Emerging Mutations in the Japanese Encephalitis Virus Envelope Protein

Japanese encephalitis virus (JEV) causes significant encephalitis across the Asia-Pacific region. Current vaccines target historical genotype III strains, but emerging genotypes,potentially driven by vaccine-mediated selective pressure, threaten vaccine effectiveness through altered envelope protein sequences that may reduce antibody cross-neutralisation. This study employed integrated sequence and structural analyses to identify E protein mutations affecting neutralising antibody binding and protein stability. The study curated JEV polyprotein sequences from NCBI, performed multiple sequence alignment, and used Shannon entropy to pinpoint highly variable positions. Mutations occurring at [≥]1% frequency within high-entropy regions were selected for analysis. From 34 initially identified mutations, four candidates were prioritized based on structural stabilization potential. Mutations were evaluated through FoldX stability predictions, molecular docking with antibody 2H4 using HADDOCK3, and molecular dynamics simulations. Binding energies were calculated using MM-GBSA analysis. Results demonstrated that all mutant E-2H4 complexes remained stable during simulations, with root-mean-square deviation plateauing after equilibration and minimal localized changes in root-mean-square fluctuation. These findings suggest that EDIII substitutions represent important candidates for further investigation to understand genotype-specific variations and inform next-generation vaccine development strategies against emerging JEV strains.

bioinformatics↗

bioRxiv2026

A PSMA-Targeted Up-conversion Nanoplatform for Deep-Tissue dual activation Photodynamic and Sonodynamic Therapy of Castration Resistant Prostate Cancer.

Photodynamic therapy (PDT) for prostate cancer is limited by the shallow penetration of visible light into deep-seated tumors. In contrast, sonodynamic therapy (SDT) enables noninvasive deep-tissue activation using ultrasound, while near-infrared photodynamic therapy (NIR-PDT) enhances tissue penetration through up-conversion-mediated activation. Based on these advantages, we developed a prostate-specific membrane antigen (PSMA)-targeted nanotheranostic platform (UCNPs@mSiO2/HPPH@TCS) to compare NIR-PDT and SDT in vitro for penetration-enhanced and targeted prostate cancer therapy. The nanoformulation consists of NaYF4:Yb3+, Er3+ up-conversion nanoparticles coated with mesoporous silica for high loading of HPPH (Photochlor), which functions as both photosensitizer and sonosensitizer, and a PSMA-targeted chitosan shell for selective tumor targeting. Physicochemical characterization confirms a uniform core-shell structure ([~]63 nm). Tissue-mimicking depth studies demonstrate that SDT and NIR-PDT achieve greater penetration than conventional 665 nm PDT in thicker tissue layers. Intracellular reactive oxygen species (ROS) analysis shows that SDT generates higher total ROS levels, whereas NIR-PDT produces greater singlet oxygen generation. Three-dimensional spheroid models further validate efficacy, demonstrating rapid spheroid collapse via apoptosis, with SDT inducing earlier apoptosis and more uniform penetration than PDT. Collectively, the results suggest SDT provides superior overall therapeutic efficacy compared with NIR-PDT, highlighting the potential of this nanoplatform for precision prostate cancer therapy.

cancer biology↗

bioRxiv2025

Neanderthal Introgressed COVID-19 Risk Locus 3p21.31 Under Positive Selection in East Asia via LZTFL1-Driven Ciliary Changes

The Neanderthal introgressed 3p21.31 locus has been repeatedly associated as a major host genetic determinant of severe COVID-19, particularly in European and South Asian populations. However, the evolutionary history and likely effector gene remain unclear. We investigated signatures of historical selection at this locus and the mechanism by which it might influence COVID-19 severity. Using 1000 Genomes Project data from diverse global populations, we applied various selection scans methods and integrated it with functional analysis. Multiple, independent lines of evidence indicate strong positive selection at 3p21.31 in East Asians. The region exceeds the 99.99th-percentile PBS threshold in EAS, shows extended ROH and the slowest LD decay among populations, and exhibits reduced nucleotide diversity and significantly negative Tajimas D, consistent with a selective sweep. XP-EHH identified a pronounced signal centred on LZTFL1. Marginal-tree reconstruction indicates the derived allele arose in modern humans and swept to high frequency in East Asia at a time consistent with an ancient corona or related virus-like epidemic [~]20,000-25,000 (20-25 Kya) years ago. LD and pathway analyses implicate a high-LD haplotype tagging LZTFL1 shows significant enrichment for cilium-assembly and BBSome-mediated cargo-targeting pathways likely causing subtle shifts in cilium number or beat frequency, in lung and airway epithelia, thereby profoundly affecting the mucus and pathogens clearance. Based on the Overall observation, we propose that after the Neanderthal introgression, East Asia went through pathogen pressure for [~]20-25 Kya old ancient coronavirus- or related virus epidemic leading to positive selection at 3p21.31locus. These findings underscore the complex interplay between ancient admixture and adaptive events linked to modern COVID-19 severity.

evolutionary biology↗

bioRxiv2025

Changes in free-roaming dog population demographics and health associated with a catch-neuter-vaccinate-release program in Jamshedpur, India

Indias large free-roaming dog populations contribute to significant human health, environmental, and social challenges. Population management strategies, such as capture-neuter-vaccinate-return (CNVR), aim to reduce dog numbers, improve their welfare, and reduce human-animal conflict. The Humane Society International, in partnership with the Animal Health Foundation, implemented a CNVR program in Jamshedpur, neutering and vaccinating over 20,000 dogs. This study evaluates the impact of this program on dog health, population structure and size. The study areas encompassed 10 sites within the Jamshedpur Metropolitan Region, including both intervention sites where CNVR was directly applied and sites without direct intervention. Data was collected from May 2014 until December 2018, including bi-annual street surveys, as well as clinical data from the dogs captured and treated. We fit logistic regression, negative binomial, and binomial mixed effects models to assess changes in dog population characteristics, health, and reproductive conditions over time in relation to the CNVR intervention. We found that, over time, the CNVR program significantly reduced the probability of dogs entering the clinic with mange, transmissible venereal tumours, and pregnant. Street surveys showed an increase in sterilised dogs, with higher proportions observed in CNVR-treated sites, although the counts of dogs observed increased overall. The age-structure of free-roaming dogs remained stable over time. In CNVR-treated areas, the probability of observing lactating female dogs decreased, whereas it increased in untreated sites. This work contributes to the growing body of knowledge investigating the impact of dog population management interventions. Continued monitoring and evaluation of CNVR programs are required to identify optimal coverage required to reduce population size effectively.

ecology↗

bioRxiv2021

Stress-responsive Long Non-coding RNA, hsrω, is a genetic modifier of JNK-dependent Intrinsic Tumor Suppression in Drosophila

Host genetics is known to influence cancer susceptibility. However, the specific candidate genes and molecular mechanisms that confer resistance remain poorly understood. Here, we demonstrate the power of haploinsufficiency screen to uncover host genetic regulators of cancer in Drosophila and identify the long noncoding RNA (lncRNA) hsr{omega}, a structural component of nuclear biomolecular condensate known as omega speckles, as a key host cancer susceptibility locus. Loss of hsr{omega} disrupts proteostasis and cell fitness, while its haploinsufficiency accelerates epithelial tumor progression driven by loss of the Lethal giant larvae (Lgl) tumor suppressor. Further validating the breadth of this screening strategy, we independently identified Drosophila STING (innate immunity) and Keap1 (oxidative stress defense) as genetic modifiers of cancer. Moreover, in humans, copy number variations (CNV) in these genes and Sat III (a functional human homolog of hsr{omega}) correlate with poor cancer prognosis, thereby revealing conserved stress pathways as potential host genetic susceptibility regulators.

cancer biology↗

bioRxiv2021

A Serpin27A-dependent Toll Signaling Underlies Host Genetics of Cancer Resistance in Drosophila

Cancer resistance varies amongst individuals, although its host genetic underpinnings remain largely elusive. Remissions of sarcomas were first reported following repeated injections of patients with mixtures of killed bacteria--Coleys toxins--a phenomenon, which was subsequently causally traced to induction of innate immunity. Here we reveal remission of Drosophila epithelial neoplasms by genetically triggered host innate immunity via Toll signaling. These neoplasms display capacities to receive and, in rare instances, induce Toll signaling. A tumor-induced and progressive Toll signaling, however, did not culminate in tumor suppression. By contrast, Drosophila hosts heterozygous for spn27A1 mutation, which constitutively produce activated Toll ligand, SpzAct, displayed comprehensive tumor remission via Toll-induced, NF-{kappa}B-mediated, tumor cell death. Our results reveal a novel node of host genetic cancer resistance via serpin-dependent Toll signaling.

cancer biology↗