Biology subjects

Rafique, A.

Publications and source records attributed to Rafique, A..

6 recordsLinked to original sources

bioRxiv2026

Maftivimab monotherapy is effective in a non-human primate model of Bundibugyo virus disease

The 2026 outbreak of Bundibugyo ebolavirus (BDBV) in the Democratic Republic of the Congo and Uganda has created an urgent need for treatments for BDBV disease, yet the only FDA-approved ebolavirus therapeutics, the monoclonal antibody (mAb) cocktail Inmazeb and the mAb Ebanga, are indicated for Zaire ebolavirus (EBOV). Maftivimab (REGN3479), the most potent neutralizing component of Inmazeb, targets ebolavirus species GPs broadly; however, how it engages BDBV GP, whether it neutralizes BDBV-2026, and whether it protects against BDBV disease in vivo are unknown. Here we show that Maftivimab binds to BDBV-2007 GP with high affinity and potently neutralizes pseudoviruses carrying GP from a 2007 reference strain and the 2026 outbreak lineage. Additionally, a cryo-electron microscopy structure of Maftivimab Fab bound to trimeric BDBV-2007 GP superimposes closely on the EBOV GP:Maftivimab complex; importantly, all GP contact residues are conserved between the 2007 and 2026 BDBV sequences. Finally, in cynomolgus macaques challenged with BDBV-2007, a single dose of Maftivimab monotherapy given 7 days after infection, after the onset of clinical disease, rescued 6 of 6 animals, whereas 5 of 6 placebo-treated animals succumbed. These findings demonstrate that Maftivimab neutralizes BDBV, binds to its epitope on BDBV GP and is efficacious in treating established BDBV disease in the macaque model. The data support its evaluation in clinical trials during the ongoing or future outbreak.

immunology↗

bioRxiv2025

PlasmidFlow: A Web-based Platform for Interactive Visualization of Plasmid-Driven Traits

Plasmids are central mediators of horizontal gene transfer (HGT), facilitating the spread of antimicrobial resistance, virulence determinants, and adaptive functions across microbial communities. Despite the availability of extensive plasmid sequencing data, visualization of plasmid-mediated traits remains hindered by reliance on static figures or coding-intensive pipelines, limiting accessibility for microbiologists and epidemiologists. We present PlasmidFlow (https://plasmidflow.metabopotential.site), an interactive, web-based platform for the exploration of plasmid-host-trait associations across ecological and clinical contexts. The system integrates structured data parsing, relational storage, and modular visualization to support real-time exploration without requiring programming expertise. Users can upload plasmid-host-trait datasets, apply environment-or trait-specific filters, and generate publication-ready Sankey diagrams, plasmid-sharing network graphs, and binary trait heatmaps with full customization of visual properties. High-resolution export in SVG, PDF, and PNG formats, along with reproducible session storage, ensures compatibility with both research and publication workflows. By combining interactivity, scalability, and reproducibility, PlasmidFlow addresses a critical gap in microbial genomics, providing a user-friendly and extensible resource for investigating plasmid-driven traits in the context of antimicrobial resistance surveillance, microbial ecology, and evolutionary biology.

microbiology↗

bioRxiv2025

Integrative Assessment of Pathogenic Bacterial Genomes: Insights from Quality Metrics

Genomic resources are increasingly being shared in public databases for reusability. Ensuring the quality of these resources is crucial, as the presence of low-quality genomes can compromise downstream analyses and propagate across databases. However, there is a lack of consistent and comprehensive assessments for such genomes in public genomic databases. This study focused on the quality assessment of 474 pathogenic bacterial genomes submitted from South Korea, with a particular emphasis on the integrative application of completeness, contiguity, and accuracy metrics. The genomes were ranked based on cumulative scores derived from individual metrics. High-ranked genomes consistently exceeded defined thresholds, including 98% completeness for complete single-copy BUSCO, less than 200 contigs, N50 values greater than 65 kb, and unmapped reads below 2%. Notably, positive and negative linear associations were observed among these quality metrics, emphasizing their integrative utilization, although the consistency across all metrics varied. The findings emphasize the importance of conducting comprehensive genome assessments and implementing stringent quality control measures in public databases to enhance the reliability and usefulness of pathogenic bacterial genomic data. By addressing these issues, we can improve the overall quality of public genomic resources and ensure their suitability for diverse downstream applications.

microbiology↗

bioRxiv2022

Structure of the Inmazeb cocktail and resistance to escape against Ebola virus

Monoclonal antibodies can provide important pre- or post-exposure protection against disease for those not yet vaccinated or in individuals that fail to mount a protective immune response after vaccination. A key concern in use of monotherapy monoclonal antibody products lies in the high risk of mutagenic escape. Inmazeb (REGN-EB3), a three-antibody cocktail against Ebola virus, demonstrated efficacy in lessening disease course and improving survival in a randomized, controlled trial. Here we present the cryoEM structure at 3.1 [A] of the Ebola virus glycoprotein, determined without symmetry averaging, in a simultaneous complex with eight Fab fragments of antibodies in the Inmazeb cocktail. This structure allows modeling of previously disordered portions of the glycan cap, maps the non-overlapping epitopes of Inmazeb, and illuminates the basis for complementary activities, as well as residues that are critical for resistance to escape by each component of this cocktail and other clinically relevant antibodies. We also provide direct evidence that, unlike monotherapy treatments, including those targeting conserved epitopes, the Inmazeb protects against the rapid emergence of EBOV escape mutants and supports the benefit of the combination approach.

biophysics↗

bioRxiv2022

Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM

The recognition of antigenic peptide-MHC (pMHC) molecules by T-cell receptors (TCR) initiates the T-cell mediated immune response. Structural characterization is key for understanding the specificity of TCR-pMHC interactions and informing the development of therapeutics. Despite the rapid rise of single particle cryoelectron microscopy (cryoEM), x-ray crystallography has remained the preferred method for structure determination of TCR-pMHC complexes. Here, we report cryoEM structures of two distinct full-length /{beta} TCR-CD3 complexes bound to their pMHC ligand, the cancer-testis antigen HLA-A2/MAGEA4 (230-239). We also determined cryoEM structures of pMHCs containing MAGEA4 (230-239) peptide and the closely related MAGEA8 (232-241) peptide in the absence of TCR, which provided a structural explanation for the MAGEA4 preference displayed by the TCRs. These findings provide insights into the TCR recognition of a clinically relevant cancer antigen and demonstrate the utility of cryoEM for high-resolution structural analysis of TCR-pMHC interactions.

biochemistry↗

bioRxiv2019

The finger 2 tip loop of Activin A is required for the formation of its non-signaling complex with ACVR1 and type II Bone Morphogenetic Protein receptors

Activin A functions in BMP signaling in two ways: it either engages ACVR1B to activate Smad2/3 signaling or binds ACVR1 to form a non-signaling complex (NSC). Although the former property has been studied extensively, the roles of the NSC remain unexplored. The genetic disorder fibrodysplasia ossificans progressiva (FOP) provides a unique window into ACVR1/Activin A signaling because in that disease Activin can either signal through FOP-mutant ACVR1 or form NSCs with wild type ACVR1. To explore the role of the NSC, we generated agonist-only Activin A muteins that activate ACVR1B but cannot form the NSC with ACVR1. Using one of these muteins we demonstrate that failure to form the NSC in FOP results in more severe disease pathology. These results provide the first evidence for a biological role for the NSC in vivo and pave the way for further exploration of the NSCs physiological role in corresponding knock-in mice. Impact StatementThe non-signaling complex formed by Activin A and ACVR1 is operant in vivo and is required to temper the degree of heterotopic ossification in the genetic disorder fibrodysplasia ossificans progressiva.

cell biology↗