Characterisation and therapeutic manipulation of Flaviviridae innate immune evasion

Lead Research Organisation: University College London
Department Name: Infection

Abstract

Flavirviridae include hepatitis C virus (HCV) and the insect transmitted viruses dengue virus (DV) and Zika virus (ZV). DV and ZV are emerging infections, spreading to new regions of the world, in part due to climate change expanding insect vector ranges. Currently around 60 million people suffer symptomatic DV infection each year with 10,000 deaths. It will be increasingly important to understand how to develop new antivirals as new infectious agents emerge and old agents spread. Cyclophilins (Cyps) are host enzymes that alter the shape of target proteins, but have poorly understood cellular functions. Critically, Cyps are widely found to act as cofactors for viral infection and HCV, DV and ZV all depend on Cyps for replication. Cells are very good at protecting themselves from infection using a variety of mechanisms termed cell autonomous innate immunity. This complex system detects incoming and replicating viruses using sensors that detect molecular patterns that are specific to the pathogen. Sensor triggering activates production interferon, which is secreted and induces expression of a whole host of antiviral proteins and pathways that potently suppress infection in nearby cells. Successful viruses must evade or antagonise these protective systems. Typically viruses hide from the sensors in a process we term cloaking. Flaviviridae hide by subverting the intracellular membrane system, cloaking their replication complexes in a membranous web. This excludes key sensors allowing unhindered RNA and viral protein production and viral assembly. Our preliminary data demonstrate that inhibiting Cyps uncloaks HCV revealing it to sensors including the RNA sensor RIG-I. This is evidenced by production of interferon when Cyp use by the virus is disturbed. Cyp inhibition is a powerful approach to developing antivirals because the antiviral effect is mediated by the host innate immune system, which is potent and difficult for the virus to escape. Targeting host factors makes the virus behave like a virus which doesn't infect humans because it activates and succumbs to innate immune defences.

Our key discovery was to find that HCV doesn't require Cyps if its target cells have a defective innate immune system. This revealed that the virus uses Cyps to evade innate immunity. Here we aim to understand exactly how Flaviviridae use Cyps to evade innate immune protective systems. We will identify the specific Cyps used and test whether our novel Cyp inhibitors can suppress replication. We will identify the viral proteins targeted by Cyps and work out what Cyps do structurally to the virus proteins to help the virus hide. Our drug series distinguishes between different viruses and we will work out how. We will test which Cyps are targeted by the active drugs to explain the antiviral specificity that we see. We will study the membranous web and viral replication compartment and see how it changes when we disturb Cyp activity. Do the sensors enter the replication compartment and get activated when Cyps are disturbed? We will also study the innate immune system and identify the active sensors that detect the virus when we reveal it. All of these aims use tried and tested techniques in use in our or collaborators' laboratories.

Our work will generate critical understanding of how host factors can protect viruses from innate immunity and how this interaction can be disturbed as a novel therapeutic or prophylactic strategy. Our goal is to generate new knowledge detailing the molecular mechanisms of the process of innate immune evasion by Flaviviridae and the consequences of disturbing it. We propose that this new knowledge and the demonstration of the tractability of host targeting strategies will be necessary before such strategies can be taken to the clinic as effective therapeutics.

Technical Summary

We have developed three series of novel cyclophilin inhibitors (CypI) and demonstrated that specific compounds activate innate immunity against hepatitis C virus (HCV) and are potent inhibitors of dengue virus (DV) and Zika virus (ZV). We will now measure replication of defined HCV/DV/ZV subgenomic replicon systems encoding luciferase and full length viruses in Cyp manipulated cells (RNAi/CRISPR or CypI) to identify the Cyps involved and the active CypI, and to define the role of innate immunity in the inhibitory process (by manipulating sensors and adapters to rescue inhibited infection). We will explain CypI antiviral specificity by correlating Cyp specificity (measured in recombinant protein binding assays) with antiviral specificity. We will examine the effect of Cyps on the viral replication compartments (confocal/electron microscopy), testing whether sensors colocalise with viral RNA/proteins on Cyp manipulation, and how host and viral proteins are relocalised when sensing is activated. We will discover which viral proteins are targeted by Cyps using binding assays between candidate proteins as well as by immunoprecipitating viral proteins and examining copurifying cellular proteins using mass spectrometry. We will determine how Cyp recruitment changes viral proteins using X-ray crystallography of Cyp-viral protein complexes. We will select virus CypI resistant mutants and characterise their sensitivity to innate immunity. We will identify the sensors and innate immune pathways activated by wild type and mutant viruses in Cyp manipulated cells. Overall, this work will define the Cyps acting as cofactors for Flaviviridae, explain how they aid in evasion of innate immune sensing, and produce a series of specific and potent inhibitors that disturb innate evasion to unleash the innate immune system against the virus as a new paradigm for antiviral prophylaxis and therapy.

Planned Impact

Here we will demonstrate how the innate immune system can be harnessed for antiviral therapy by drugging the protective cloaking mechanisms viruses use to hide from innate immune sensors. We have already developed host-targeting cyclophilin inhibitors (CypI), which effectively inhibit emerging viruses dengue virus (DV) and Zika virus (ZV), as well as hepatitis C virus (HCV), an established and worldwide human infection. Critically, our preliminary data illustrate the involvement of innate immunity in anti-HCV activity of these molecules and we anticipate innate immune involvement for DV/ZV too. Detailing how innate immunity is activated against infection and how these molecules can be developed as effective antivirals provides a new paradigm for anti-infectives. We expect this strategy to be widely applicable, as all infectious agents must evade host defences through related evasion and cloaking mechanisms. The generality of our approach is illustrated by the literature that demonstrates that CypI act against a huge range of untreatable viruses.

Importantly, our preliminary data demonstrate some compounds with broad antiviral specificity inhibiting HCV, DV and ZV and other molecules with antiviral specificity inhibiting only a single virus. By explaining this specificity, through the experiments proposed, this work could facilitate the development of broad and narrow specificity inhibitors. This is important because broad specificity inhibitors are not always preferable due to the risk of inadvertently selecting resistance against a different drug/pathogen combination. Our results will detail mechanistically how specificity is determined, allowing its management. Our work is also expected to explain drug resistance, its likelihood and its mechanisms. Beneficiaries will therefore include all those who benefit from the increased understanding of development of specific and broad specificity antivirals.

Should our research lead to the establishment of CypI as effective antivirals, then the beneficiaries will include two large populations (i) everybody who takes the new drugs to treat infection and (ii) everyone who uses them as prophylactics. DV currently infects 60 millions people per year and kills 10,000. Given the range of viruses inhibited by CypI, the numbers of individuals eventually treated with inhibitors developed based on the science discoveries proposed herein could be enormous. As our inhibitory strategy targets innate cloaking mechanisms, our molecules only activate innate sensing in the presence of the virus. This has the effect of making the virus behave like a virus that is not adapted to evade innate sensing, and therefore replicate, in that particular host. Thus, our antiviral strategy could protect treated individuals from becoming infected in the first place, through a similar mechanism that protects hosts from infection naturally. By describing a mechanism that is different to the classical approach of developing inhibitors of viral enzymes, we will open new avenues of research that could lead to enormous steps forward in inhibiting pathogenic infection in humans and animals as well as developing effective prophylactics for infection.

Our work will also benefit those studying and developing antivirals in general. Our observation that antivirals work more effectively in cells that are competent for innate immune sensing will be an important consideration, even when developing direct acting antivirals. This is because viral enzymes also have roles in evasion of innate immunity. Thus, their inhibition can make inhibited virus sensitive to innate immune sensing, meaning that antiviral effects are best studied in systems where innate immunity is active. Our work will detail how this can be achieved and demonstrate the difference in the inhibitory effects in innate competent and innate defective systems. In this way, our work will contribute to the improvement of antiviral discovery in general.

Publications

10 25 50
 
Title Selected pieces from John Walter's Capsid displayed at The Suttie Arts Space, Aberdeen Royal Infirmary 
Description Exhibition of three paintings from the Co-Factors series, part of 'CAPSID' which was funded by a large arts Award from the Wellcome Trust to John Walter for collaborative work with Greg Towers 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2020 
Impact CAPSID was created as part of the collaboration between John Walter and Greg funded by the Wellcome Trust Large Arts Award and was exhibited at 'HOME' in Manchester and the LGP London's Galleries. The exhibitions were enormously popular and resulted in one of HOME's most successful exhibitions to date. The exhibitions have made research into HIV, it's life cycle and interactions with it's host accessible to the general public and help to demistify the research we do. 
URL http://www.ghat-art.org.uk/john-walter-artist-talk-co-factors/
 
Description ADV THERAPIE: Novel IFITM3 inhibitors as transduction enhancers for stem cell gene therapy
Amount £99,964 (GBP)
Funding ID CiC006 
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 09/2019 
End 02/2021
 
Description COVID related extension to 'CHARACTERISATION OF INNATE IMMUNE DNA SENSING AND VIRAL EVASION STRATEGIES'
Amount £101,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2020 
End 03/2021
 
Description Characterisation and therapeutic manipulation of Flaviviridae innate immune evasion
Amount £421,323 (GBP)
Funding ID MR/S023380/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2019 
End 09/2022
 
Description Development of IFITM inhibitors as transduction enhancers to facilitate efficient human Stem Cell Gene Therapy
Amount £150,000 (GBP)
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2021 
End 01/2024
 
Description Establishing mechanism for Covid-19 inflammatory disease
Amount £55,000 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 07/2020 
End 04/2021
 
Description G2P-UK; A National Virology Consortium to address phenotypic consequences of SARSCoV-2 genomic variation
Amount £3,136,000 (GBP)
Funding ID MR/W005611/1 
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 02/2021 
End 07/2023
 
Description Pathogens Travel Award for CSH
Amount SFr. 800 (CHF)
Organisation MPDI journals 
Sector Private
Country Switzerland
Start 05/2019 
End 05/2019
 
Description Studying lentiviruses to understand mechanisms, regulation and consequences of nucleic acid sensing
Amount £1,809,720 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2021 
End 02/2026
 
Description TOWERS WT VACATION: The role of cGAS localisation in sensing and restricting HIV
Amount £2,768 (GBP)
Funding ID 218411/Z/19/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2019 
End 08/2019
 
Description What is special about pandemic HIV-1? How capsid cofactor interactions regulate DNA synthesis, innate immune detection and pandemic potential
Amount £2,110,344 (GBP)
Funding ID 214344/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2019 
End 12/2023
 
Description travel award from the Journal of General Virology to attend the RIVR meeting
Amount £200 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 01/2019 
End 01/2019
 
Title ChromaClade: combined visualisation of phylogenetic and sequence data 
Description Background Studying site-specific amino acid frequencies by eye can reveal biologically significant variability and lineage-specific adaptation. This so-called 'sequence gazing' often informs bioinformatics and experimental research. But it is important to also account for the underlying phylogeny, since similarities may be due to common descent rather than selection pressure, and because it is important to distinguish between founder effects and convergent evolution. We set out to combine phylogenetic and sequence data to produce evolutionarily insightful visualisations. Results We present ChromaClade, a convenient tool with a graphical user-interface that works in concert with popular tree viewers to produce colour-annotated phylogenies highlighting residues found in each taxon and at each site in a sequence alignment. Colouring branches according to residues found at descendent tips also quickly identifies lineage-specific residues and those internal branches where key substitutions have occurred. We demonstrate applications of ChromaClade to human immunodeficiency virus and influenza A virus datasets, illustrating cases of conservative, adaptive and convergent evolution. Conclusions We find this to be a powerful approach for visualising site-wise residue distributions and detecting evolutionary patterns, especially in large datasets. ChromaClade is available for Windows, macOS and Unix or Linux; program executables and source code are available at github.com/chrismonit/chroma_clade. Background Visually inspecting molecular sequence data - so called 'sequence gazing' - can be extremely insightful. Sites that are evolutionarily conserved may be crucial for a protein's structure and function, while variation may indicate divergent selective constraints in separate groups. For molecular biologists these observations can inspire hypotheses to be tested by point mutation experiments that examine the functional effect of the differences, while for bioinformaticians they can motivate more formal computational analysis. The approach is vastly improved by taking account of the organisms' phylogenetic relationships, firstly because some sequences will be more similar due to common descent rather than evolutionary constraint and secondly because this helps identify evolutionary trends, such as characteristics gained or lost in particular clades. At present there is no convenient, automated way to visualise phylogenetic and sequence data simultaneously. Implementation ChromaClade annotates and colours taxon names in phylogenetic trees according to the residues found in the corresponding sequence alignment. For each site in an alignment, ChromaClade annotates taxon names with residue letter codes and a residue-specific hexadecimal red/green/blue colour code that can be recognised by popular tree viewers, such as FigTree [1] or Archaeopteryx [2]. The annotated trees, whose topologies are identical to the original, are saved to a single file to be loaded into the tree viewer, meaning the data for each site can be inspected by simply looking through the set of coloured trees in the viewer. Residue-specific colouring can also be applied to branches whose descendent taxa have the same residue. This helps classify lineages by their unique amino acids and illustrates how deep within the phylogenetic history substitutions have arisen. Written in Python, ChromaClade is suitable for all major operating systems and has graphical and command line interfaces available; convenient application bundles are available for Windows and macOS. ChromaClade makes use of the Biopython and Biopython.Phylo libraries [3]. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact Used to identify determinant of HIV pandemicity (manuscript in preparation) Used to identify homoplasy in SARS-CoV2 project underway 
URL https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-019-1518-9#Abs1
 
Description Development of antiviral inhibitors 
Organisation University College London
Department Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution We contribute to design and testing of new antiviral molecules and investigate mechanism
Collaborator Contribution David Selwood and his lab design and synthesise the new antiviral molecules
Impact Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells. Jimenez-Moyano E, Ruiz A, Kløverpris HN, Rodriguez-Plata MT, Peña R, Blondeau C, Selwood DL, Izquierdo-Useros N, Moris A, Clotet B, Goulder P, Towers GJ, Prado JG. J Virol. 2016 Sep 12;90(19):8552-62. doi: 10.1128/JVI.00819-16. Print 2016 Oct 1. PMID: 27440884 Culley S, Towers GJ, Selwood DL, Henriques R, Grove J. Infection Counter: Automated Quantification of in Vitro Virus Replication by Fluorescence Microscopy. Viruses. 2016 Jul 21;8(7). pii: E201. doi: 10.3390/v8070201. Warne J, Pryce G, Hill JM, Shi X, Lennerås F, Puentes F, Kip M, Hilditch L, Walker P, Simone MI, Chan AW, Towers GJ, Coker AR, Duchen MR, Szabadkai G, Baker D, Selwood DL. Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis. J Biol Chem. 2016 Feb 26;291(9):4356-73. doi: 10.1074/jbc.M115.700385. Epub 2015 Dec 17. Rasaiyaah, J., C. P. Tan, A. J. Fletcher, A. J. Price, C. Blondeau, L. Hilditch, D. A. Jacques, D. L. Selwood, L. C. James, M. Noursadeghi and G. J. Towers. 2013. HIV-1 evades innate immune recognition through specific co-factor recruitment. Nature (2013) doi:10.1038/nature12769 Wellcome Trust Senior Biomedical Research Fellowship 2nd Renewal "Characterisation of innate immune DNA sensing and viral evasion strategies" 1/10/15-30/09/20 £2,121,162 Wellcome Trust Collaborator Award "What's so special about pandemic HIV. How capsid cofactor interactions regulate DNA synthesis, innate immune detection and pandemic potential" PI with collaborators Leo James LMB Cambridge, David Selwood UCL, David Jacques and Till Boecking University of New South Wales. 1/3/2019-28/2/2024 £2,677,937 (£1,027,334 to UCL) Confidence in Collaboration Award Advanced Therapeutics "CiC006 - Novel IFITM3 inhibitors as transduction enhancers for stem cell gene therapy" £99,965 09/08/2019-08/08/2020 ERC Advanced Grant "Characterisation and Manipulation of Primate Lentiviral Innate Immune Evasion Strategies" PI with co-applicant Prof David Selwood, Wolfson Institute of Biomedical Sciences, UCL, Feb 2014-Jan 2019 €2,499,643 National Institute of Health Research UCLH/UCL Biomedical Research Centre Grant Development of broad specificity anti-viral drugs 15/8/2016-14/8/2019 £199,555 UCL Therapeutic Innovation Fund Grant "A small molecule screen for inhibitors of DNA sensing" Co-applicant with applicant Prof David Selwood, Wolfson Institute of Biomedical Sciences, UCL, 2015-2016 £59,387 MRC Confidence in Concept Award "Development of small molecules that inhibit viral replication by triggering innate immune responses" with co-applicant Prof David Selwood Wolfson Institute of Biomedical Sciences UCL, 01/04/2013-31/08/2014 £100,000 UCL Business Proof of Concept Award Co-Applicant with PI Prof David Selwood Wolfson Institute of Biomedical Sciences UCL. A new treatment for viral infection that triggers the innate immune response.1/08/2013 £54,996 Disciplines are molecular virology and chemistry
 
Description Restriction Factor Structure Function 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution We have characterised host restriction factor relationships and evolution by collaborating with Leo James at the laboratory for Molecular Biology. Leo solves structures and performs biophysical measurements of protein/protein interactions and we characterise and assay mutant behavior thereby learning mechanistic molecular details of action and evolution.
Collaborator Contribution The James lab has solved crystal structures of restriction factors and viral proteins and performed many biophysical and chemistry experiments allowing us to understand the mechanistic details of restriction factor virus interactions.
Impact We have copublished PMIDs 21045130, 20808866, 19767750, 19073742 Collaboration is multidiciplinary in that we are molecular virologists and James is a biophysicist and protein crystallographer
Start Year 2007
 
Description The Role of Capsid Cofactor Interactions 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution We investigate how Capsid Cofactor interactions regulate innate immune detection and pandemic potential
Collaborator Contribution Till Boecking, David Jacques and their labs investigate how Capsid Cofactor interactions regulate DNA synthesis. Leo James investigates the structural function of capsid.
Impact WELLCOME TRUST Collaborative grant: 'What is special about pandemic HIV-1? How capsid cofactor interactions regular DNA synthesis, innate immune detection and pandemic potential' 1 March 2019 to 29 February 2024. £525,166.00 Trivalent RING Assembly on Retroviral Capsids Activates TRIM5 Ubiquitination and Innate Immune Signaling. Fletcher AJ, Vaysburd M, Maslen S, Zeng J, Skehel JM, Towers GJ, James LC. Cell Host Microbe. 2018 Dec 12;24(6):761-775.e6. doi: 10.1016/j.chom.2018.10.007. Epub 2018 Nov 29. PMID:30503508. IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis. Mallery DL, Márquez CL, McEwan WA, Dickson CF, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, Saiardi A, Böcking T, James LC. Elife. 2018 May 31;7. pii: e35335. doi: 10.7554/eLife.35335. PMID:29848441 HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC. Nature. 2016 Aug 18;536(7616):349-53. Epub 2016 Aug 10. PMID: 27509857
 
Description The Role of Capsid Cofactor Interactions 
Organisation University of New South Wales
Department School of Medical Sciences
Country Australia 
Sector Academic/University 
PI Contribution We investigate how Capsid Cofactor interactions regulate innate immune detection and pandemic potential
Collaborator Contribution Till Boecking, David Jacques and their labs investigate how Capsid Cofactor interactions regulate DNA synthesis. Leo James investigates the structural function of capsid.
Impact WELLCOME TRUST Collaborative grant: 'What is special about pandemic HIV-1? How capsid cofactor interactions regular DNA synthesis, innate immune detection and pandemic potential' 1 March 2019 to 29 February 2024. £525,166.00 Trivalent RING Assembly on Retroviral Capsids Activates TRIM5 Ubiquitination and Innate Immune Signaling. Fletcher AJ, Vaysburd M, Maslen S, Zeng J, Skehel JM, Towers GJ, James LC. Cell Host Microbe. 2018 Dec 12;24(6):761-775.e6. doi: 10.1016/j.chom.2018.10.007. Epub 2018 Nov 29. PMID:30503508. IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis. Mallery DL, Márquez CL, McEwan WA, Dickson CF, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, Saiardi A, Böcking T, James LC. Elife. 2018 May 31;7. pii: e35335. doi: 10.7554/eLife.35335. PMID:29848441 HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC. Nature. 2016 Aug 18;536(7616):349-53. Epub 2016 Aug 10. PMID: 27509857
 
Title Chromaclade 
Description Phylogenetic tree analysis 
Type Of Technology Webtool/Application 
Year Produced 2019 
Impact A new way to examine phylogenetic trees 
URL https://github.com/chrismonit/chroma_clade
 
Description 'Outbreak!' run at Mossbourne Community Academy and Mossbourne Victoria Park 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 pupils participate in an 'Outbreak!' organised by us at their school or run in the teaching labs at UCL. Designed and run by Lucy Thorne. Pupils role play as diagnostic scientists charged with identifying the causative agent of an outbreak of disease at their school. The students analyse medical observation charts and undertake tests of mock patient samples to identify a virus and confirm their findings with further 'sequencing'. They conclude with defending their diagnosis at a press conference. Older groups of students will also undertake a colourmetric test to identify a possible zoonotic aspect to the Outbreak.
Year(s) Of Engagement Activity 2020
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events
 
Description Article in WIRED 'Does Covid-killing UV tech work?' 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interviewed by WIRED magazine about the safety of UV-C wands and their effectivity. The aim was to inform people about the considerations required to make sure a wand is effective and safe
Year(s) Of Engagement Activity 2021
URL https://www.wired.co.uk/article/does-uv-tech-actually-work
 
Description Article in WIRED 'We asked coronavirus experts what summer 2021 will be like' 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Input into popular magazine article discussing realistic expectations of the summer in 2021, the possibility of travel, sporting and music events and the role vacine will play. The aim being to inform a wide range of people.
Year(s) Of Engagement Activity 2021
URL https://www.wired.co.uk/article/summer-plans-coronavirus-experts
 
Description Booklet - A Guide to Coronavirus for friends and family 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Dr Lucy Thorne has written a guide with Greg Towers to address the questions about COVID-19 we have had from friends and family.
Year(s) Of Engagement Activity 2020
URL https://www.ucl.ac.uk/towers-lab/sites/towers-lab/files/coronavirus-guide-24062020_.pdf
 
Description Interview by iNews - Coronavirus latest: Hopes for new Covid-19 treatment after promising antiviral drug development 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed by iNews about promising results from our work with the Krogen lab at UCSF testing Aplidin's antiviral properties. The aim was to raise the profile fo the lab and inform the public about the research ongoing into drugs agaisnt COVID
Year(s) Of Engagement Activity 2021
URL https://inews.co.uk/news/science/new-covid-treatment-after-promising-antiviral-drug-development-8455...
 
Description Interviewed by Tom Swarbrick on LBC about COVID19 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Interviewed by Tom Swarbrick on LBC about the SARS-CoV-2 Kent varient, why varients emerge and how likely they are to sweep the world.
Year(s) Of Engagement Activity 2021
URL https://www.lbc.co.uk/radio/presenters/tom-swarbrick/virologist-kent-covid-variant-sweep-the-world/
 
Description Mossbourne Community Academy and Mossbourne Victoria Park 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 pupils participate in an 'Outbreak!' organised by us at their school or run in the teaching labs at UCL. Designed and run by Lucy Thorne. Pupils role play as diagnostic scientists charged with identifying the causative agent of an outbreak of disease at their school. The students analyse medical observation charts and undertake tests of mock patient samples to identify a virus and confirm their findings with further 'sequecing'. They conclude with defending their diagnosis at a press conference. Older groups of students will also undertake a colourmetric test to identify a possible zoonotic aspect to the Outbreak.
Year(s) Of Engagement Activity 2019,2020
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events#outbreak