Explanipedia

A modified cyclosporine enhances lentivector transduction ex vivo and in vivo by degrading IFITM3 Open

Dara Annett, Kate L. Morling, Bethan J. Critchley, Brent Graham, Valeria Pingitore , et al. · 2025

Intrinsic innate immune barriers have evolved to suppress viral infection and can reduce effective gene delivery in gene therapy. We have developed BG147, a novel cyclosporine A analogue, optimised via structure-guided design to prevent in…

Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV Open

Lydia S. Newton, Clara Gathmann, Sophie Ridewood, Robert J. Smith, Andre J. Wijaya , et al. · 2025

Targeting host proteins that are crucial for viral replication offers a promising antiviral strategy. We have designed and characterised antiviral PROteolysis TArgeting Chimeras (PROTACs) targeting the human protein cyclophilin A (CypA), a…

Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants Open

Ann‐Kathrin Reuschl, Lucy Thorne, Matthew V. X. Whelan, Roberta Ragazzini, Wilhelm Furnon , et al. · 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve distinct globally dominant sub…

SARS-CoV-2 variants evolve convergent strategies to remodel the host response Open

Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Benjamin J. Polacco, Lucy Thorne, Manisha R. Ummadi , et al. · 2023

Synthetic PROTACs based on a depsipeptide macrocycle selectively degrade cyclophilin A and inhibit HIV-1 Open

Clara Gathmann, Lydia S. Newton, Sophie Ridewood, Robert J. Smith, Thomas W. Hornsby , et al. · 2023

We have designed and characterised PROteolysis TArgeting Chimeras (PROTACs) active against the human protein cyclophilin A (CypA), a viral cofactor required for efficient replication of a series of unrelated viruses. Our cyclophilin PROTAC…

SARS-CoV-2 evolution influences GBP and IFITM sensitivity Open

Dejan Mesner, Ann‐Kathrin Reuschl, Matthew V. X. Whelan, Taylor Bronzovich, Tafhima Haider , et al. · 2023

SARS-CoV-2 spike requires proteolytic processing for viral entry. A polybasic furin-cleavage site (FCS) in spike, and evolution toward an optimized FCS by dominant variants of concern (VOCs), are linked to enhanced infectivity and transmis…

SARS-CoV-2 variant biology: immune escape, transmission and fitness Open

Alessandro M. Carabelli, Thomas P. Peacock, Lucy Thorne, William T. Harvey, Joseph Hughes , et al. · 2023

SARS-CoV-2 Variants Evolve Convergent Strategies to Remodel the Host Response Open

Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Benjamin J. Polacco, Lucy Thorne, Manisha R. Ummadi , et al. · 2023

Global landscape of the host response to SARS-CoV-2 variants reveals viral evolutionary trajectories Open

Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Benjamin J. Polacco, Lucy Thorne, Manisha R. Ummadi , et al. · 2022

A series of SARS-CoV-2 variants of concern (VOCs) have evolved in humans during the COVID-19 pandemic—Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic and genomic analyses during infection to understand the molecular …

Evolutionary remodelling of N‐terminal domain loops fine‐tunes SARS‐CoV‐2 spike Open

Diego Cantoni, Matthew J Murray, Mphatso D. Kalemera, Samuel J. Dicken, Lenka Stejskal , et al. · 2022

Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants Open

Ann‐Kathrin Reuschl, Lucy Thorne, Matthew V. X. Whelan, Roberta Ragazzini, Wilhelm Furnon , et al. · 2022

SARS-CoV-2 adaptation to humans is evidenced by the emergence of variants of concern (VOCs) with distinct genotypes and phenotypes that facilitate immune escape and enhance transmission frequency. Most recently Omicron subvariants have eme…

Publisher Correction: Evolution of enhanced innate immune evasion by SARS-CoV-2 Open

Lucy Thorne, Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Lorena Zuliani‐Alvarez, Benjamin J. Polacco , et al. · 2022

SARS-CoV-2 Spike evolution influences GBP and IFITM sensitivity Open

Dejan Mesner, Ann‐Kathrin Reuschl, Matthew V. X. Whelan, Taylor Bronzovich, Tafhima Haider , et al. · 2022

SARS-CoV-2 spike requires proteolytic processing for viral entry. The presence of a polybasic furin-cleavage site (FCS) in spike, and evolution towards an optimised FCS by dominant variants of concern (VOCs), are linked to enhanced infecti…

Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19 Open

José F. Varona, Pedro Landete, José A. López-Martín, Vicente Estrada, Roger Paredes , et al. · 2022

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially …

Evolution of enhanced innate immune evasion by SARS-CoV-2 Open

Lucy Thorne, Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Lorena Zuliani‐Alvarez, Benjamin J. Polacco , et al. · 2021

Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection Open

Constantina Borg, Aminu S. Jahun, Lucy Thorne, Frédéric Sorgeloos, Dalan Bailey , et al. · 2021

Murine norovirus (MNV) is widely used as a model for studying norovirus biology. While MNV isolates vary in their pathogenesis, infection of immunocompetent mice mostly results in persistent infection. The ability of a virus to establish a…

SARS‐CoV‐2 sensing by RIG‐I and MDA5 links epithelial infection to macrophage inflammation Open

Lucy Thorne, Ann‐Kathrin Reuschl, Lorena Zuliani‐Alvarez, Matthew V. X. Whelan, Jane Turner , et al. · 2021

Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant Open

Lucy Thorne, Mehdi Bouhaddou, Ann‐Kathrin Reuschl, Lorena Zuliani‐Alvarez, Benjamin J. Polacco , et al. · 2021

Emergence of SARS-CoV-2 variants, including the globally successful B.1.1.7 lineage, suggests viral adaptations to host selective pressures resulting in more efficient transmission. Although much effort has focused on Spike adaptation for …

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization Open

José F. Varona, Pedro Landete, José A. López-Martín, Vicente Estrada, Roger Paredes , et al. · 2021

Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention …

Characterisation of B.1.1.7 and Pangolin coronavirus spike provides insights on the evolutionary trajectory of SARS-CoV-2 Open

Samuel J. Dicken, Matthew J Murray, Lucy Thorne, Ann‐Kathrin Reuschl, Calum Forrest , et al. · 2021

The recent emergence of SARS-CoV-2 variants with increased transmission, pathogenesis and immune resistance has jeopardised the global response to the COVID-19 pandemic. Determining the fundamental biology of viral variants and understandi…

Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant Open

Ann‐Kathrin Reuschl, Lucy Thorne, Lorena Zuliani‐Alvarez, Mehdi Bouhaddou, Kirsten Obernier , et al. · 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide and massive societal and economic burden. Recently, a new variant of SARS-CoV-2, know…

SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation Open

Lucy Thorne, Ann‐Kathrin Reuschl, Lorena Zuliani‐Alvarez, Matthew V. X. Whelan, Mahdad Noursadeghi , et al. · 2020

Summary SARS-CoV-2 infection causes broad-spectrum immunopathological disease, exacerbated by inflammatory co-morbidities. A better understanding of mechanisms underpinning virus-associated inflammation is required to develop effective the…

HIV-1 Vpr antagonizes innate immune activation by targeting karyopherin-mediated NF-κB/IRF3 nuclear transport Open

Hataf Khan, Rebecca P. Sumner, Jane Rasaiyaah, Choon Ping Tan, Maria T. Rodriguez‐Plata , et al. · 2020

HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. HIV-1 evades innate immune sensing through encapsidated DNA synthesis and encodes accessory genes that antagon…

Author response: HIV-1 Vpr antagonizes innate immune activation by targeting karyopherin-mediated NF-κB/IRF3 nuclear transport Open

Hataf Khan, Rebecca P. Sumner, Jane Rasaiyaah, Choon Ping Tan, Maria T. Rodriguez‐Plata , et al. · 2020

Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection [Primary data] Open

Constantina Borg, Aminu S. Jahun, Lucy Thorne, Frédéric Sorgeloos, Dalan Bailey , et al. · 2020

Primary data underlying journal article titled "Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection"

Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection [Primary data] Open

Constantina Borg, Aminu S. Jahun, Lucy Thorne, Frédéric Sorgeloos, Dalan Bailey , et al. · 2020

Primary data underlying journal article titled "Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection"

Murine norovirus virulence factor 1 (VF1) protein contributes to viral fitness during persistent infection Open

Constantina Borg, Aminu S. Jahun, Lucy Thorne, Frédéric Sorgeloos, Dalan Bailey , et al. · 2019

Background Murine norovirus (MNV) is widely used as a model for studying norovirus biology. While MNV isolates vary in their pathogenesis, infection of immunocompetent mice mostly results in persistent infection. The ability of a virus to …

Cyclosporine H Overcomes Innate Immune Restrictions to Improve Lentiviral Transduction and Gene Editing In Human Hematopoietic Stem Cells Open

Carolina Petrillo, Lucy Thorne, Giulia Unali, Giulia Schiroli, Anna M. Giordano , et al. · 2018

Targeting macrophage- and intestinal epithelial cell-specific microRNAs against norovirus restricts replication in vivo Open

Lucy Thorne, Jia Lu, Yasmin Chaudhry, Dalan Bailey, Ian Goodfellow · 2018

Until recently, our understanding of the cellular tropism of human norovirus (HuNoV), a major cause of viral gastroenteritis, has been limited. Immune cells and intestinal epithelial cells (IECs) have been proposed as targets of HuNoV repl…

miR-155 induction is a marker of murine norovirus infection but does not contribute to control of replication in vivo Open

Lucy Thorne, Jia Lu, Yasmin Chaudhry, Ian Goodfellow · 2018

Background: Due to their role in fine-tuning cellular protein expression, microRNAs both promote viral replication and contribute to antiviral responses, for a range of viruses. The interactions between norovirus and the microRNA machinery…

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