Evaluation of Hepatitis B core-related antigen (HBcrAg) as a biomarker in cohorts from the United Kingdom and South Africa.

Objectives: We set out to evaluate Hepatitis B core-related antigen (HBcrAg) as a proxy for hepatitis B (HBV) viral load (VL) and liver disease in two different population settings.

Methods: We undertook a cross-sectional retrospective observational study using samples and data from adults living with chronic HBV infection from the United Kingdom (UK, n=142) and South Africa (SA, n=211). We assessed HBcrAg distribution, relationship with other biomarkers, and risk stratification performance, applying point of care test (POCT) thresholds.

Hepatitis C virus cascade of care among adults in Sindh province, Pakistan: Findings from 2019-2020 household sero-survey.

Pakistan has the largest national burden of hepatitis C virus (HCV) infections (9.8 million). High levels of testing and treatment are needed to achieve HCV elimination, but little data exists on this in Pakistan.

A Multiscale Computational Study for the Identification of Novel Inhibitors Targeting Tau-Tubulin Kinase 1 (TTBK1) in Alzheimer's Disease.

Introduction: Excessive phosphorylation of tau protein by the tau-tubulin kinase 1 (TTBK1) enzyme is implicated in the pathogenesis of several neurodegenerative diseases. Based on a comprehensive literature review and availability of the co-crystal structure of TTBK1 in complex inhibitor (pdb id 4BTK), we designed a multiscale computational approach to identify novel hits from the ZINC13 chemical library.

Methods: The High-Throughput Virtual Screening (HTVS) of the ZINC13 database (containing 13,195,609 molecules) was carried out against TTBK1 protein (PDB id 4BTK).

Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease.

Hepatitis C virus (HCV) exists as a heterogenous quasispecies, but the phenotypic consequences of viral variability are widely unexplored. Here we identified a replication enhancing domain (ReED) in nonstructural protein 5A conferring high replication fitness to clinical isolates. Accumulation of mutations in the ReED mediates high genome replication capacity.

Treatment options to support the elimination of hepatitis C: an open-label, factorial, randomised controlled non-inferiority trial.

Background: WHO recommends treating hepatitis C infection with one of three antiviral combinations for 8-12 weeks. No randomised trials have compared these regimens, and high cure rates might be achievable with shorter durations of therapy. We aimed to compare sofosbuvir-daclatasvir with sofosbuvir-velpatasvir, and to evaluate potential novel treatment strategies.

Genetically distinct within-host subpopulations of hepatitis C virus persist after Direct-Acting Antiviral treatment failure.

Analysis of viral genetic data has previously revealed distinct within-host population structures in both untreated and interferon-treated chronic hepatitis C virus (HCV) infections. While multiple subpopulations persisted during the infection, each subpopulation was observed only intermittently. However, it was unknown whether similar patterns were also present after Direct-Acting Antiviral (DAA) treatment, where viral populations were often assumed to go through narrow bottlenecks.

A putative hepatitis B virus sequence motif associated with hepatocellular carcinoma in South African adults.

Introduction And Objectives: Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). In African populations, HCC frequently presents at an advanced stage with poor outcomes. We applied whole genome sequencing (WGS) to compare HBV genomes in individuals with and without HCC.

Whole genome sequencing of hepatitis B virus using tiled amplicon (HEPTILE) and probe based enrichment on Illumina and Nanopore platforms.

Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below the threshold required to generate full genomes using current sequencing methods. We developed two pan-genotypic viral enrichment methods, using probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS. We demonstrate using mock samples that both enrichment methods are pan-genotypic (genotypes A-J).

Inhibitory Potency of Chlorogenic Acid from Apple Cider Vinegar Against Alzheimer's Disease: Molecular Docking and Dynamics Validation.

Objective: The primary cause of memory loss is Alzheimer's disease (AD). Recent studies have shown that natural compounds like apple cider vinegar (ACV) have anti-Alzheimer's capabilities. Essential components of ACV, such as gallic acid and chlorogenic acid, may be in charge of the drug's pharmacological effects.

Identifying Novel Inhibitors for Dengue NS2B-NS3 Protease by Combining Topological similarity, Molecular Dynamics, MMGBSA and SiteMap Analysis.

Introduction: DENV NS2B-NS3 protease inhibitors were designed based upon the reference molecule, 4-(1,3-dioxoisoindolin-2-yl)-N-(4-ethylphenyl) benzenesulfonamide, reported by our team with the aim to optimize lead compound via rational approach. Top five best scoring molecules with zinc ids ZINC23504872, ZINC48412318, ZINC00413269, ZINC13998032 and ZINC75249613 bearing 'pyrimidin-4(3H)-one' basic scaffold have been identified as a promising candidate against DENV protease enzyme.

Methods: The shape and electrostatic complementary between identified HITs and reference molecules were found to be Tanimotoshape 0.

Castanet: a pipeline for rapid analysis of targeted multi-pathogen genomic data.

Motivation: Target enrichment strategies generate genomic data from multiple pathogens in a single process, greatly improving sensitivity over metagenomic sequencing and enabling cost-effective, high-throughput surveillance and clinical applications. However, uptake by research and clinical laboratories is constrained by an absence of computational tools that are specifically designed for the analysis of multi-pathogen enrichment sequence data. Here we present an analysis pipeline, Castanet, for use with multi-pathogen enrichment sequencing data.

Inference of Host-Pathogen Interaction Matrices from Genome-Wide Polymorphism Data.

Host-pathogen coevolution is defined as the reciprocal evolutionary changes in both species due to genotype × genotype (G×G) interactions at the genetic level determining the outcome and severity of infection. While co-analyses of hosts and pathogen genomes (co-genome-wide association studies) allow us to pinpoint the interacting genes, these do not reveal which host genotype(s) is/are resistant to which pathogen genotype(s). The knowledge of this so-called infection matrix is important for agriculture and medicine.

Current strategies to address data scarcity in artificial intelligence-based drug discovery: A comprehensive review.

Artificial intelligence (AI) has played a vital role in computer-aided drug design (CADD). This development has been further accelerated with the increasing use of machine learning (ML), mainly deep learning (DL), and computing hardware and software advancements. As a result, initial doubts about the application of AI in drug discovery have been dispelled, leading to significant benefits in medicinal chemistry.

Prevalence of resistance-associated viral variants to the HIV-specific broadly neutralising antibody 10-1074 in a UK bNAb-naïve population.

Broadly neutralising antibodies (bNAbs) targeting HIV show promise for both prevention of infection and treatment. Among these, 10-1074 has shown potential in neutralising a wide range of HIV strains. However, resistant viruses may limit the clinical efficacy of 10-1074.

Targeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the leading cause of hospitalisation for respiratory infection in young children. RSV disease severity is known to be age-dependent and highest in young infants, but other correlates of severity, particularly the presence of additional respiratory pathogens, are less well understood. In this study, nasopharyngeal swabs were collected from two cohorts of RSV-positive infants <12 months in Spain, the UK, and the Netherlands during 2017-20.

Generative artificial intelligence in drug discovery: basic framework, recent advances, challenges, and opportunities.

There are two main ways to discover or design small drug molecules. The first involves fine-tuning existing molecules or commercially successful drugs through quantitative structure-activity relationships and virtual screening. The second approach involves generating new molecules through drug design or inverse quantitative structure-activity relationship.

Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes.

The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072).

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

Background: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection.

Dual targeting in prostate cancer with phytoconstituents as a potent lead: a computational approach for novel drug discovery.

Prostate Cancer (PCa) is an abnormal cell growth within the prostate. This condition is the second most widespread malignancy in elderly males and one of the most frequently diagnosed life-threatening conditions. The Androgen receptor signaling pathway played a crucial role in the initiation and spread to increase the risk of PCa.

Genotyping and population characteristics of the China Kadoorie Biobank.

The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history.

An enrichment protocol and analysis pipeline for long read sequencing of the hepatitis B virus transcriptome.

Hepatitis B virus (HBV) is one of the smallest human DNA viruses and its 3.2 Kb genome encodes multiple overlapping open reading frames, making its viral transcriptome challenging to dissect. Previous studies have combined quantitative PCR and Next Generation Sequencing to identify viral transcripts and splice junctions, however the fragmentation and selective amplification used in short read sequencing precludes the resolution of full length RNAs.