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1. Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform

Author

Bojkova, Denisa, Reus, Philipp, Panosch, Leona, Bechtel, Marco, Rothenburger, Tamara, Kandler, Joshua D., Pfeiffer, Annika, Wagner, Julian U.G., Shumliakivska, Mariana, Dimmeler, Stefanie, Olmer, Ruth, Martin, Ulrich, Vondran, Florian W.R., Toptan, Tuna, Rothweiler, Florian, Zehner, Richard, Rabenau, Holger F., Osman, Karen L., Pullan, Steven T., Carroll, Miles W., Stack, Richard, Ciesek, Sandra, Wass, Mark N., Michaelis, Martin, and Cinatl, Jindrich, Jr.

Published
2023
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4. Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

Author

Ryan, Kathryn A., Bewley, Kevin R., Fotheringham, Susan A., Slack, Gillian S., Brown, Phillip, Hall, Yper, Wand, Nadina I., Marriott, Anthony C., Cavell, Breeze E., Tree, Julia A., Allen, Lauren, Aram, Marilyn J., Bean, Thomas J., Brunt, Emily, Buttigieg, Karen R., Carter, Daniel P., Cobb, Rebecca, Coombes, Naomi S., Findlay-Wilson, Steve J., Godwin, Kerry J., Gooch, Karen E., Gouriet, Jade, Halkerston, Rachel, Harris, Debbie J., Hender, Thomas H., Humphries, Holly E., Hunter, Laura, Ho, Catherine M. K., Kennard, Chelsea L., Leung, Stephanie, Longet, Stephanie, Ngabo, Didier, Osman, Karen L., Paterson, Jemma, Penn, Elizabeth J., Pullan, Steven T., Rayner, Emma, Skinner, Oliver, Steeds, Kimberley, Taylor, Irene, Tipton, Tom, Thomas, Stephen, Turner, Carrie, Watson, Robert J., Wiblin, Nathan R., Charlton, Sue, Hallis, Bassam, Hiscox, Julian A., Funnell, Simon, Dennis, Mike J., Whittaker, Catherine J., Catton, Michael G., Druce, Julian, Salguero, Francisco J., and Carroll, Miles W.

Published
2021
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6. Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant

Author

Ryan, Kathryn A., primary, Bewley, Kevin R., additional, Watson, Robert J., additional, Burton, Christopher, additional, Carnell, Oliver, additional, Cavell, Breeze E., additional, Challis, Amy, additional, Coombes, Naomi S., additional, Davies, Elizabeth R., additional, Edun-Huges, Jack, additional, Emery, Kirsty, additional, Fell, Rachel, additional, Fotheringham, Susan A., additional, Gooch, Karen E., additional, Gowan, Kathryn, additional, Handley, Alastair, additional, Harris, Debbie J., additional, Hesp, Richard, additional, Hunter, Laura, additional, Humphreys, Richard, additional, Johnson, Rachel, additional, Kennard, Chelsea, additional, Knott, Daniel, additional, Lister, Sian, additional, Morley, Daniel, additional, Ngabo, Didier, additional, Osman, Karen L., additional, Paterson, Jemma, additional, Penn, Elizabeth J., additional, Pullan, Steven T., additional, Richards, Kevin S., additional, Summers, Sian, additional, Thomas, Stephen R., additional, Weldon, Thomas, additional, Wiblin, Nathan R., additional, Rayner, Emma L., additional, Vipond, Richard T., additional, Hallis, Bassam, additional, Salguero, Francisco J., additional, Funnell, Simon G. P., additional, and Hall, Yper, additional

Published
2023
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8. Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform

Author

Bojkova, Denisa, primary, Reus, Philipp, additional, Panosch, Leona, additional, Bechtel, Marco, additional, Rothenburger, Tamara, additional, Kandler, Joshua, additional, Pfeiffer, Annika, additional, Wagner, Julian U.G., additional, Shumliakivska, Mariana, additional, Dimmeler, Stefanie, additional, Olmer, Ruth, additional, Martin, Ulrich, additional, Vondran, Florian, additional, Toptan, Tuna, additional, Rothweiler, Florian, additional, Zehner, Richard, additional, Rabenau, Holger, additional, Osman, Karen L., additional, Pullan, Steven T., additional, Carroll, Miles, additional, Stack, Richard, additional, Ciesek, Sandra, additional, Wass, Mark N, additional, Michaelis, Martin, additional, and Cinatl, Jindrich, additional

Published
2022
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9. Natural History of Sudan ebolavirus to Support Medical Countermeasure Development

Author

Carbonnelle, Caroline, primary, Moroso, Marie, additional, Pannetier, Delphine, additional, Godard, Sabine, additional, Mély, Stéphane, additional, Thomas, Damien, additional, Duthey, Aurélie, additional, Jourjon, Ophélie, additional, Lacroix, Orianne, additional, Labrosse, Béatrice, additional, Raoul, Hervé, additional, Osman, Karen L., additional, Salguero, Francisco J., additional, Hall, Yper, additional, Sabourin, Carol L., additional, Merchlinsky, Michael J., additional, Long, James P., additional, Parish, Lindsay A., additional, and Wolfe, Daniel N., additional

Published
2022
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10. Identification of novel antiviral drug candidates using an optimized SARS-CoV-2 phenotypic screening platform

Author

Bojkova, Denisa, Reus, Philipp, Panosch, Leona, Bechtel, Marco, Rothenburger, Tamara, Kandler, Joshua D., Pfeiffer, Annika Eby, Wagner, Julian Uwe Gabriel, Shumliakivska, Mariana, Dimmeler, Stefanie, Olmer, Ruth Maria, Martin, Ulrich, Vondran, Florian, Toptan, Tuna, Rothweiler, Florian, Zehner, Richard, Rabenau, Holger, Osman, Karen L., Pullan, Steven T., Carroll, Miles, Stack, Richard, Ciesek, Sandra, Wass, Mark N., Michaelis, Martin, Cinatl, Jindrich, Bojkova, Denisa, Reus, Philipp, Panosch, Leona, Bechtel, Marco, Rothenburger, Tamara, Kandler, Joshua D., Pfeiffer, Annika Eby, Wagner, Julian Uwe Gabriel, Shumliakivska, Mariana, Dimmeler, Stefanie, Olmer, Ruth Maria, Martin, Ulrich, Vondran, Florian, Toptan, Tuna, Rothweiler, Florian, Zehner, Richard, Rabenau, Holger, Osman, Karen L., Pullan, Steven T., Carroll, Miles, Stack, Richard, Ciesek, Sandra, Wass, Mark N., Michaelis, Martin, and Cinatl, Jindrich

Abstract

Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a read-out for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in a broad range of cell culture models, independently of cytopathogenic effect formation. Compared to other cell culture models, the Caco-2 subline Caco-2-F03 displayed superior performance, as it possesses a stable SARS-CoV-2 susceptible phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of PHGDH, CLK-1, and CSF1R. The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the HK2 inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false positive hits.

Published
2022

12. Convalescence from prototype SARS-CoV-2 protects Syrian hamsters from disease caused by the Omicron variant

Author

Ryan, Kathryn A., primary, Watson, Robert J., additional, Bewley, Kevin R., additional, Burton, Christopher, additional, Carnell, Oliver, additional, Cavell, Breeze E., additional, Challis, Amy, additional, Coombes, Naomi S., additional, Emery, Kirsty, additional, Fell, Rachel, additional, Fotheringham, Susan A., additional, Gooch, Karen E., additional, Gowan, Kathryn, additional, Handley, Alastair, additional, Harris, Debbie J., additional, Humphreys, Richard, additional, Johnson, Rachel, additional, Knott, Daniel, additional, Lister, Sian, additional, Morley, Daniel, additional, Ngabo, Didier, additional, Osman, Karen L., additional, Paterson, Jemma, additional, Penn, Elizabeth J., additional, Pullan, Steven T., additional, Richards, Kevin S., additional, Shaik, Imam, additional, Summers, Sian, additional, Thomas, Stephen R., additional, Weldon, Thomas, additional, Wiblin, Nathan R., additional, Vipond, Richard, additional, Hallis, Bassam, additional, Funnell, Simon G. P., additional, and Hall, Yper, additional

Published
2021
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13. Corrigendum: Pneumococcal vaccine impacts on the population genomics of non-typeable haemophilus influenzae: (Microbial Genomics 2021; 9, 10.1099/mgen.0.000209)

Author

Cleary, David W., Devine, Vanessa T., Morris, Denise E., Osman, Karen L., Gladstone, Rebecca A., Bentley, Stephen D., Faust, Saul N., and Clarke, Stuart C.

Abstract

There was a change in the author names in the published article. The new list should read: David W. Cleary1,2, Vanessa T. Devine3, Denise E. Morris1, Karen L. Osman1, Rebecca A. Gladstone4, Stephen D. Bentley4, Saul N. Faust1,5, Stuart C. Clarke1,2,6 1Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. 2NIHR Southampton Biomedical Research Centre, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 3Northern Ireland Centre for Stratified Medicine and Clinical Translational Research Innovation Centre, Londonderry, UK. 4Pathogen Genomics, Wellcome Trust Sanger Institute, UK. 5NIHR Southampton Clinical Research Facility, University Hospital Southampton Foundation NHS Trust, Southampton, UK. 6Global Health Research Institute, University of Southampton, Southampton, UK.

Published
2021

14. Diagnosis of SARS-CoV-2 Infection with LamPORE, a High-Throughput Platform Combining Loop-Mediated Isothermal Amplification and Nanopore Sequencing

Author

Peto, Leon, primary, Rodger, Gillian, additional, Carter, Daniel P., additional, Osman, Karen L., additional, Yavuz, Mehmet, additional, Johnson, Katie, additional, Raza, Mohammad, additional, Parker, Matthew D., additional, Wyles, Matthew D., additional, Andersson, Monique, additional, Justice, Anita, additional, Vaughan, Alison, additional, Hoosdally, Sarah, additional, Stoesser, Nicole, additional, Matthews, Philippa C., additional, Eyre, David W., additional, Peto, Timothy E. A., additional, Carroll, Miles W., additional, de Silva, Thushan I., additional, Crook, Derrick W., additional, Evans, Cariad M., additional, and Pullan, Steven T., additional

Published
2021
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16. B.1.1.7 became the dominant variant in Lebanon

Author

Younes, Mahmoud, primary, Hamze, Kassem, additional, Carter, Daniel P., additional, Osman, Karen L., additional, Vipond, Richard, additional, Carroll, Miles, additional, Pullan, Steven T., additional, Nassar, Hassan, additional, Mohamad, Nada, additional, Makki, Mohamad, additional, Ghadar, Maysaa, additional, Nguewa, Paul, additional, and Sater, Fadi Abdel, additional

Published
2021
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17. Diagnosis of SARS-CoV-2 infection with LamPORE, a high-throughput platform combining loop-mediated isothermal amplification and nanopore sequencing

Author

Peto, Leon, primary, Rodger, Gillian, additional, Carter, Daniel P, additional, Osman, Karen L, additional, Yavuz, Mehmet, additional, Johnson, Katie, additional, Raza, Mohammad, additional, Parker, Matthew D, additional, Wyles, Matthew D, additional, Andersson, Monique, additional, Justice, Anita, additional, Vaughan, Alison, additional, Hoosdally, Sarah, additional, Stoesser, Nicole, additional, Matthews, Philippa C, additional, Eyre, David W, additional, Peto, Timothy EA, additional, Carroll, Miles W, additional, de Silva, Thushan I, additional, Crook, Derrick W, additional, Evans, Cariad M, additional, and Pullan, Steven T, additional

Published
2020
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18. Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge

Author

Ryan, Kathryn A., primary, Bewley, Kevin R., additional, Fotheringham, Susan A., additional, Brown, Phillip, additional, Hall, Yper, additional, Marriott, Anthony C., additional, Tree, Julia A., additional, Allen, Lauren, additional, Aram, Marilyn J., additional, Brunt, Emily, additional, Buttigieg, Karen R., additional, Cavell, Breeze E., additional, Carter, Daniel P., additional, Cobb, Rebecca, additional, Coombes, Naomi S., additional, Godwin, Kerry J., additional, Gooch, Karen E., additional, Gouriet, Jade, additional, Halkerston, Rachel, additional, Harris, Debbie J., additional, Humphries, Holly E., additional, Hunter, Laura, additional, Ho, Catherine M. K., additional, Kennard, Chelsea L., additional, Leung, Stephanie, additional, Ngabo, Didier, additional, Osman, Karen L., additional, Paterson, Jemma, additional, Penn, Elizabeth J., additional, Pullan, Steven T., additional, Rayner, Emma, additional, Slack, Gillian S., additional, Steeds, Kimberley, additional, Taylor, Irene, additional, Tipton, Tom, additional, Thomas, Stephen, additional, Wand, Nadina I., additional, Watson, Robert J., additional, Wiblin, Nathan R., additional, Charlton, Sue, additional, Hallis, Bassam, additional, Hiscox, Julian A., additional, Funnell, Simon, additional, Dennis, Mike J., additional, Whittaker, Catherine J., additional, Catton, Michael G., additional, Druce, Julian, additional, Salguero, Francisco J., additional, and Carroll, Miles W., additional

Published
2020
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19. The adhesins of non-typeable Haemophilus influenzae

Author

Osman, Karen L., Jefferies, Johanna M., Woelk, Christopher H., Cleary, David W., and Clarke, Stuart C.

Subjects
otorhinolaryngologic diseases
Abstract

Introduction: Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen of the respiratory tract and the greatest contributor to invasive Haemophilus disease. Additionally, in children, NTHi is responsible for the majority of otitis media (OM) which can lead to chronic infection and hearing loss. In adults, NTHi infection in the lungs is responsible for the onset of acute exacerbations in chronic obstructive pulmonary disease (COPD). Unfortunately, there is currently no vaccine available to protect against NTHi infections. Areas covered: NTHi uses an arsenal of adhesins to colonise the respiratory epithelium. The adhesins also have secondary roles that aid in the virulence of NTHi, including mechanisms that avoid immune clearance, adjust pore size to avoid antimicrobial destruction, form micro-colonies and invoke phase variation for protein mediation. Bacterial adhesins can also be ideal antigens for subunit vaccine design due to surface exposure and immunogenic capabilities. Expert commentary: The host-pathogen interactions of the NTHi adhesins are not fully investigated. The relationship between adhesins and the extracellular matrix (ECM) play a part in the success of NTHi colonisation and virulence by immune evasion, migration and biofilm development. Further research into these immunogenic proteins would further our understanding and enable a basis for better combatting NTHi disease.

Published
2018

22. Outbreak of Ralstonia pickettii associated with contamination of saline products distributed internationally, the United Kingdom, 2024.

Author

Saunders M, Weaver A, Stretch R, Jeyaratnam D, Mirfenderesky M, Elliott D, Patterson C, Williams D, Kenna DT, Turton J, Osman KL, Turton JF, Brown CS, and Elston J

Subjects
Humans, United Kingdom epidemiology, Saline Solution, Bacteremia epidemiology, Bacteremia microbiology, Australia epidemiology, Drug Contamination, Male, Disease Outbreaks, Ralstonia pickettii isolation & purification, Ralstonia pickettii genetics, Gram-Negative Bacterial Infections epidemiology, Gram-Negative Bacterial Infections microbiology
Abstract

We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.

Published
2024
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23. Pneumococcal vaccine impacts on the population genomics of non-typeable Haemophilus influenzae.

Author

Cleary DW, Devine VT, Morris DE, Osman KL, Gladstone RA, Bentley SD, Faust SN, and Clarke SC

Subjects
Biosynthetic Pathways genetics, Child, Preschool, Drug Resistance, Bacterial genetics, Haemophilus influenzae classification, Haemophilus influenzae drug effects, Haemophilus influenzae genetics, Humans, Infant, Infant, Newborn, Mutation, Recombination, Genetic, Streptococcus pneumoniae isolation & purification, United Kingdom, Whole Genome Sequencing, Haemophilus influenzae isolation & purification, Pneumococcal Vaccines
Abstract

The implementation of pneumococcal conjugate vaccines (PCVs) has led to a decline in vaccine-type disease. However, there is evidence that the epidemiology of non-typeable Haemophilus influenzae (NTHi) carriage and disease can be altered as a consequence of PCV introduction. We explored the epidemiological shifts in NTHi carriage using whole genome sequencing over a 5-year period that included PCV13 replacement of PCV7 in the UK's National Immunization Programme in 2010. Between 2008/09 and 2012/13 (October to March), nasopharyngeal swabs were taken from children <5 years of age. Significantly increased carriage post-PCV13 was observed and lineage-specific associations with Streptococcus pneumoniae were seen before but not after PCV13 introduction. NTHi were characterized into 11 discrete, temporally stable lineages, congruent with current knowledge regarding the clonality of NTHi. The increased carriage could not be linked to the expansion of a particular clone and different co-carriage dynamics were seen before PCV13 implementation when NTHi co-carried with vaccine serotype pneumococci. In summary, PCV13 introduction has been shown to have an indirect effect on NTHi epidemiology and there exists both negative and positive, distinct associations between pneumococci and NTHi. This should be considered when evaluating the impacts of pneumococcal vaccine design and policy.

Published
2018
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24. The adhesins of non-typeable Haemophilus influenzae.

Author

Osman KL, Jefferies JM, Woelk CH, Cleary DW, and Clarke SC

Subjects
Adult, Animals, Biofilms, Child, Haemophilus Infections microbiology, Haemophilus Infections prevention & control, Haemophilus influenzae isolation & purification, Host-Pathogen Interactions, Humans, Otitis Media epidemiology, Otitis Media microbiology, Pulmonary Disease, Chronic Obstructive epidemiology, Pulmonary Disease, Chronic Obstructive microbiology, Respiratory Mucosa microbiology, Virulence, Adhesins, Bacterial metabolism, Haemophilus Infections epidemiology, Haemophilus influenzae pathogenicity
Abstract

Introduction: Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen of the respiratory tract and the greatest contributor to invasive Haemophilus disease. Additionally, in children, NTHi is responsible for the majority of otitis media (OM) which can lead to chronic infection and hearing loss. In adults, NTHi infection in the lungs is responsible for the onset of acute exacerbations in chronic obstructive pulmonary disease (COPD). Unfortunately, there is currently no vaccine available to protect against NTHi infections. Areas covered: NTHi uses an arsenal of adhesins to colonise the respiratory epithelium. The adhesins also have secondary roles that aid in the virulence of NTHi, including mechanisms that avoid immune clearance, adjust pore size to avoid antimicrobial destruction, form micro-colonies and invoke phase variation for protein mediation. Bacterial adhesins can also be ideal antigens for subunit vaccine design due to surface exposure and immunogenic capabilities. Expert commentary: The host-pathogen interactions of the NTHi adhesins are not fully investigated. The relationship between adhesins and the extracellular matrix (ECM) play a part in the success of NTHi colonisation and virulence by immune evasion, migration and biofilm development. Further research into these immunogenic proteins would further our understanding and enable a basis for better combatting NTHi disease.

Published
2018
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