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1. WHALING IN THE EARLY DECADES OF THE AUSTRALIAN COLONIES.

Author

Stuart, David

Abstract

In considering the American contacts with the colony of New South Wales in its early decades, my previous article in this journal concentrated on American sealing and the role of individual Americans in the colonial industry. It concluded that the Americans' impact on the colony combined elements of both competition and co-operation with the colonial sealing industry. This second article addresses the history of recorded visits by American whaling vessels to ports in the colonies and the influence of individual Americans, focusing on two who made a significant impact on colonial whaling, Captain Eber Bunker, whose Australian whaling experience spanned 35 years, and Richard Hazard, an African-American who became prominent in Van Diemen's Land as a skilled mariner and harpooner in the 1820s. It aims to give a fuller picture of the extent of British, colonial and American whaling before 1830, and to address how the exaggerated view of whaling as an aspect of early American engagement with the colonies first arose and why it continues to resonate. [ABSTRACT FROM AUTHOR]

Published
2024

2. Persistence of SARS-CoV-2 antibodies over 18 months following infection: UK Biobank COVID-19 Serology Study

Author

Bešević, Jelena, Lacey, Ben, Callen, Howard, Omiyale, Wemimo, Conroy, Megan, Feng, Qi, Crook, Derrick W, Doherty, Nicola, Ebner, Daniel, Eyre, David W, Fry, Dan, Horn, Edward, Jones, E Yvonne, Marsden, Brian D, Peto, Tim E A, Starkey, Fenella, Stuart, David, Welsh, Samantha, Wood, Natasha, Young, Alan, Young, Allen, Effingham, Mark, Collins, Rory, Holliday, Jo, and Allen, Naomi

Abstract

BackgroundLittle is known about the persistence of antibodies after the first year following SARS-CoV-2 infection. We aimed to determine the proportion of individuals that maintain detectable levels of SARS-CoV-2 antibodies over an 18-month period following infection.MethodsPopulation-based prospective study of 20 000 UK Biobank participants and their adult relatives recruited in May 2020. The proportion of SARS-CoV-2 cases testing positive for immunoglobulin G (IgG) antibodies against the spike protein (IgG-S), and the nucleocapsid protein (IgG-N), was calculated at varying intervals following infection.ResultsOverall, 20 195 participants were recruited. Their median age was 56 years (IQR 39–68), 56% were female and 88% were of white ethnicity. The proportion of SARS-CoV-2 cases with IgG-S antibodies following infection remained high (92%, 95% CI 90%–93%) at 6 months after infection. Levels of IgG-N antibodies following infection gradually decreased from 92% (95% CI 88%–95%) at 3 months to 72% (95% CI 70%–75%) at 18 months. There was no strong evidence of heterogeneity in antibody persistence by age, sex, ethnicity or socioeconomic deprivation.ConclusionThis study adds to the limited evidence on the long-term persistence of antibodies following SARS-CoV-2 infection, with likely implications for waning immunity following infection and the use of IgG-N in population surveys.

Published
2024
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5. Oxidative Cycloaddition Reactions of Arylboron Reagents via a One-pot Formal Dehydroboration Sequence

Author

Karandikar, Shubhendu S., Metze, Bryan E., Roberts, Riley A., and Stuart, David R.

Abstract

Arylboron compounds are widely available and synthetically useful reagents in which the boron group is typically substituted. Herein, we show that the boron group and ortho-hydrogen atom are substituted in a formal cycloaddition reaction. This transformation is enabled by a one-pot sequence involving diaryliodonium and aryne intermediates. The scope of arylboron reagents and arynophiles is demonstrated, and the method is applied to the formal synthesis of an investigational drug candidate.

Published
2023
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9. Un trono dividido: El origen y los movimientos de la Banca Jeroglífica 1 de Ixtutz, Guatemala

Author

Carter, Nicholas, Reyes, Mara Antonieta, Stuart, David, Houston, Stephen, Lukach, Katharine, and O'Neil, Megan

Abstract

Aquí presentamos el descubrimiento de una banca jeroglífica esculpida del sitio maya de Ixtutz, Petén, Guatemala. Analizamos la inscripción jeroglífica en la banca y discutimos la historia del objecto en el contexto de su producción, su desmantelamiento y reutilización subsecuente, y la remoción de unas piezas del sitio. Mostramos que dos bloques inscritos de caliza, uno de ellos en una colección privada en Bruselas y el otro en el Los Angeles County Museum of Art, Los Angeles, California, pertenecen al mismo trono, y llamamos para su repatriación voluntaria a Guatemala.

Published
2022
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10. A Great and Rising Nation: Naval Exploration and Global Empire in the Early US Republic.

Author

Stuart, David

Abstract

"A Great and Rising Nation: Naval Exploration and Global Empire in the Early US Republic" by Michael A. Verney explores the role of US naval expeditions in the nation's process of imperialization in the 19th century. The book focuses on seven antebellum naval expeditions to illustrate the multi-dimensional nature of US imperialist policy. The author argues that these expeditions were instrumental in shaping the nation's emergence as a great power. However, some aspects of the book's argument, such as the assertion of racialist ideology, are seen as tenuous or overstated. [Extracted from the article]

Published
2024

11. Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines

Author

Wei, Jia, Pouwels, Koen B., Stoesser, Nicole, Matthews, Philippa C., Diamond, Ian, Studley, Ruth, Rourke, Emma, Cook, Duncan, Bell, John I., Newton, John N., Farrar, Jeremy, Howarth, Alison, Marsden, Brian D., Hoosdally, Sarah, Jones, E. Yvonne, Stuart, David I., Crook, Derrick W., Peto, Tim E. A., Walker, A. Sarah, and Eyre, David W.

Abstract

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable.

Published
2022
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12. Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: a global perspective

Author

Halawa, Sarah, Pullamsetti, Soni S., Bangham, Charles R. M., Stenmark, Kurt R., Dorfmüller, Peter, Frid, Maria G., Butrous, Ghazwan, Morrell, Nick W., de Jesus Perez, Vinicio A., Stuart, David I., O’Gallagher, Kevin, Shah, Ajay M., Aguib, Yasmine, and Yacoub, Magdi H.

Abstract

The lungs are the primary target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with severe hypoxia being the cause of death in the most critical cases. Coronavirus disease 2019 (COVID-19) is extremely heterogeneous in terms of severity, clinical phenotype and, importantly, global distribution. Although the majority of affected patients recover from the acute infection, many continue to suffer from late sequelae affecting various organs, including the lungs. The role of the pulmonary vascular system during the acute and chronic stages of COVID-19 has not been adequately studied. A thorough understanding of the origins and dynamic behaviour of the SARS-CoV-2 virus and the potential causes of heterogeneity in COVID-19 is essential for anticipating and treating the disease, in both the acute and the chronic stages, including the development of chronic pulmonary hypertension. Both COVID-19 and chronic pulmonary hypertension have assumed global dimensions, with potential complex interactions. In this Review, we present an update on the origins and behaviour of the SARS-CoV-2 virus and discuss the potential causes of the heterogeneity of COVID-19. In addition, we summarize the pathobiology of COVID-19, with an emphasis on the role of the pulmonary vasculature, both in the acute stage and in terms of the potential for developing chronic pulmonary hypertension. We hope that the information presented in this Review will help in the development of strategies for the prevention and treatment of the continuing COVID-19 pandemic.

Published
2022
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13. Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study

Author

Närhi, Fiina, Moonesinghe, S Ramani, Shenkin, Susan D, Drake, Thomas M, Mulholland, Rachel H, Donegan, Cara, Dunning, Jake, Fairfield, Cameron J, Girvan, Michelle, Hardwick, Hayley E, Ho, Antonia, Leeming, Gary, Nguyen-Van-Tam, Jonathan S, Pius, Riinu, Russell, Clark D, Shaw, Catherine A, Spencer, Rebecca G, Turtle, Lance, Openshaw, Peter J M, Baillie, J Kenneth, Harrison, Ewen M, Semple, Malcolm G, Docherty, Annemarie B, Baillie, J Kenneth, Semple, Malcolm G, Openshaw, Peter JM, Carson, Gail, Alex, Beatrice, Andrikopoulos, Petros, Bach, Benjamin, Barclay, Wendy S, Bogaert, Debby, Chand, Meera, Chechi, Kanta, Cooke, Graham S, da Silva Filipe, Ana, de Silva, Thushan, Docherty, Annemarie B, dos Santos Correia, Gon¸alo, Dumas, Marc-Emmanuel, Dunning, Jake, Fletcher, Tom, Green, Christopher A, Greenhalf, William, Griffin, Julian, Gupta, Rishi K, Harrison, Ewen M, Hiscox, Julian A, Ho, Antonia YW, Horby, Peter W, Ijaz, Samreen, Khoo, Say, Klenerman, Paul, Law, Andrew, Lewis, Matthew, Liggi, Sonia, Lim, Wei Shen, Maslen, Lynn, Mentzer, Alexander J, Merson, Laura, Meynert, Alison M, Moore, Shona C, Noursadeghi, Mahdad, Olanipekun, Michael, Osagie, Anthonia, Palmarini, Massimo, Palmieri, Carlo, Paxton, William A, Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L, Russell, Clark D, Sancho-Shimizu, Vanessa, Sands, Caroline, Scott, Janet T, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Swann, Olivia V, Takats, Zoltan, Takis, Panteleimon, Tedder, Richard S, Thompson, AA Roger, Thomson, Emma C, Thwaites, Ryan S, Turtle, Lance CW, Zambon, Maria, Hardwick, Hayley, Donohue, Chloe, Griffiths, Fiona, Oosthuyzen, Wilna, Donegan, Cara, Spencer, Rebecca G, Norman, Lisa, Pius, Riinu, Drake, Thomas M, Fairfield, Cameron J, Knight, Stephen R, Mclean, Kenneth A, Murphy, Derek, Shaw, Catherine A, Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Plotkin, Daniel, Lee, James, Leeming, Gary, Law, Andrew, Wham, Murray, Clohisey, Sara, Hendry, Ross, Scott-Brown, James, Shaw, Victoria, McDonald, Sarah E, Keating, Seán, Ahmed, Katie A., Armstrong, Jane A, Ashworth, Milton, Asiimwe, Innocent G, Bakshi, Siddharth, Barlow, Samantha L, Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin WA, Clark, Jordan J, Clarke, Emily A, Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis WS, Foster, Terry, Garcia-Dorival, Isabel, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L, Jones, Christopher B, Jones, Trevor R, Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A, Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S, Middleton, Joanna, Mitchell, Joyce, Moore, Shona C, Murphy, Ellen G, Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E, Shears, Rebecca K, Small, Benjamin, Subramaniam, Krishanthi S, Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Doce Carracedo, Alejandra, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, McCafferty, Sarah, Clark, Richard, Fawkes, Angie, Morrice, Kirstie, Maclean, Alan, Wrobel, Nicola, Donelly, Lorna, Coutts, Audrey, Hafezi, Katarzyna, MacGillivray, Louise, Gilchrist, Tammy, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin L., Alegria, Ana, Allen, Sam, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Berry, Colin, Best, Nicola, Bothma, Pieter, Chadwick, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, Drummond, Andrew, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B, Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, Norris, Lillian, O'Shea, Matthew K., Otahal, Igor, Ostermann, Marlies, Pais, Mark, Palmieri, Carlo, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Singh Pooni, Jagtur, Planche, Tim, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ruge, Bobby, Ryan, Brendan, Saluja, Taranprit, Schmid, Matthias, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Vallotton, Nick, Vancheeswaran, Rama, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Sarah, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wootton, Daniel G, Workman, Andrew, Yates, Bryan, and Young, Peter

Abstract

Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.

Published
2022
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17. Powering up battery building.

Author

Stuart, David

Subjects
ELECTRIC vehicle batteries, PHOTOMETRIC stereo, ELECTRIC vehicle charging stations, COMPUTER vision
Published
2022

23. Characterisation of in-hospital complications associated with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol UK: a prospective, multicentre cohort study

Author

Drake, Thomas M, Riad, Aya M, Fairfield, Cameron J, Egan, Conor, Knight, Stephen R, Pius, Riinu, Hardwick, Hayley E, Norman, Lisa, Shaw, Catherine A, McLean, Kenneth A, Thompson, A A Roger, Ho, Antonia, Swann, Olivia V, Sullivan, Michael, Soares, Felipe, Holden, Karl A, Merson, Laura, Plotkin, Daniel, Sigfrid, Louise, de Silva, Thushan I, Girvan, Michelle, Jackson, Clare, Russell, Clark D, Dunning, Jake, Solomon, Tom, Carson, Gail, Olliaro, Piero, Nguyen-Van-Tam, Jonathan S, Turtle, Lance, Docherty, Annemarie B, Openshaw, Peter JM, Baillie, J Kenneth, Harrison, Ewen M, Semple, Malcolm G, Baillie, J Kenneth, Semple, Malcolm G, Openshaw, Peter JM, Carson, Gail, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S, Bogaert, Debby, Chand, Meera, Cooke, Graham S, Docherty, Annemarie B, Dunning, Jake, da Silva Filipe, Ana, Fletcher, Tom, Green, Christopher A, Harrison, Ewen M, Hiscox, Julian A, Ho, Antonia YW, Horby, Peter W, Ijaz, Samreen, Khoo, Say, Klenerman, Paul, Law, Andrew, Lim, Wei Shen, Mentzer, Alexander J, Merson, Laura, Meynert, Alison M, Noursadeghi, Mahdad, Moore, Shona C, Palmarini, Massimo, Paxton, William A, Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L, Russell, Clark D, Sancho-Shimizu, Vanessa, Scott, Janet T, de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Tedder, Richard S, Thomson, Emma C, Thompson, AA Roger, Thwaites, Ryan S, Turtle, Lance CW, Gupta, Rishi K, Palmieri, Carlo, Swann, Olivia V, Zambon, Maria, Dumas, Marc-Emmanuel, Griffin, Julian, Takats, Zoltan, Chechi, Kanta, Andrikopoulos, Petros, Osagie, Anthonia, Olanipekun, Michael, Liggi, Sonia, Lewis, Matthew, dos Santos Correia, Gonçalo, Sands, Caroline, Takis, Panteleimon, Maslen, Lynn, Hardwick, Hayley, Donohue, Chloe, Griffiths, Fiona, Oosthuyzen, Wilna, Norman, Lisa, Pius, Riinu, Drake, Thomas M, Fairfield, Cameron J, Knight, Stephen R, Mclean, Kenneth A, Murphy, Derek, Shaw, Catherine A, Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Plotkin, Daniel, Lee, James, Leeming, Gary, Law, Andrew, Wham, Murray, Clohisey, Sara, Hendry, Ross, Scott-Brown, James, Greenhalf, William, Shaw, Victoria, McDonald, Sarah E, Keating, Seán, Ahmed, Katie A., Armstrong, Jane A, Ashworth, Milton, Asiimwe, Innocent G, Bakshi, Siddharth, Barlow, Samantha L, Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin WA, Clark, Jordan J, Clarke, Emily A, Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis WS, Foster, Terry, Garcia-Dorival, Isabel, Greenhalf, William, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L, Jones, Christopher B, Jones, Trevor R, Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A, Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S, Middleton, Joanna, Mitchell, Joyce, Moore, Shona C, Murphy, Ellen G, Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E, Shears, Rebecca K, Small, Benjamin, Subramaniam, Krishanthi S, Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Doce Carracedo, Alejandra, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, Wrobel, Nicola, McCafferty, Sarah, Morrice, Kirstie, MacLean, Alan, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin L., Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Chadwick, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, Drummond, Andrew, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B, Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, Norris, Lillian, O'Shea, Matthew K., Otahal, Igor, Ostermann, Marlies, Pais, Mark, Palmieri, Carlo, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Singh Pooni, Jagtur, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Vallotton, Nick, Vancheeswaran, Rama, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Sarah, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wootton, Daniel G, Workman, Andrew, Yates, Bryan, and Young, Peter

Abstract

COVID-19 is a multisystem disease and patients who survive might have in-hospital complications. These complications are likely to have important short-term and long-term consequences for patients, health-care utilisation, health-care system preparedness, and society amidst the ongoing COVID-19 pandemic. Our aim was to characterise the extent and effect of COVID-19 complications, particularly in those who survive, using the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK.

Published
2021
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24. Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

Author

Allen, Joel D., Chawla, Himanshi, Samsudin, Firdaus, Zuzic, Lorena, Shivgan, Aishwary Tukaram, Watanabe, Yasunori, He, Wan-ting, Callaghan, Sean, Song, Ge, Yong, Peter, Brouwer, Philip J. M., Song, Yutong, Cai, Yongfei, Duyvesteyn, Helen M. E., Malinauskas, Tomas, Kint, Joeri, Pino, Paco, Wurm, Maria J., Frank, Martin, Chen, Bing, Stuart, David I., Sanders, Rogier W., Andrabi, Raiees, Burton, Dennis R., Li, Sai, Bond, Peter J., and Crispin, Max

Abstract

A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.

Published
2021
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25. Risk of adverse outcomes in patients with underlying respiratory conditions admitted to hospital with COVID-19: a national, multicentre prospective cohort study using the ISARIC WHO Clinical Characterisation Protocol UK

Author

Bloom, Chloe I, Drake, Thomas M, Docherty, Annemarie B, Lipworth, Brian J, Johnston, Sebastian L, Nguyen-Van-Tam, Jonathan S, Carson, Gail, Dunning, Jake, Harrison, Ewen M, Baillie, J Kenneth, Semple, Malcolm G, Cullinan, Paul, Openshaw, Peter J M, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S, Bogaert, Debby, Chand, Meera, Cooke, Graham S, Filipe, Ana da, Fletcher, Tom, Green, Christoper A, Harrison, Ewen M, Hiscox, Julian A, Ho, Antonia Ying, Horby, Peter W, Ijaz, Samreen, Khoo, Saye, Klenerman, Paul, Law, Andrew, Lim, Wei Shen, Mentzer, Alexander J, Merson, Laura, Meynert, Alison M, Noursadeghi, Mahdad, Moore, Shona C, Palmarini, Massimo, Paxton, William A, Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L, Russell, Clark D, Sancho-Shimizu, Vanessa, Scott, Janet T, Silva, Thushan de, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Tedder, Richard S, Thomson, Emma C, Thompson, AA Roger, Thwaites, Ryan S, Turtle, Lance CW, Zambon, Maria, Hardwick, Hayley, Donohue, Chloe, Lyons, Ruth, Griffiths, Fiona, Oosthuyzen, Wilna, Norman, Lisa, Pius, Riinu, Fairfield, Cameron J, Knight, Stephen R, Mclean, Kenneth A, Murphy, Derek, Shaw, Catherine A, Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Clohisey, Sara, Hendry, Ross, Scott-Brown, James, Greenhalf, William, Shaw, Victoria, McDonald, Sara, Keating, Seán, Ahmed, Katie A., Armstrong, Jane A, Ashworth, Milton, Asiimwe, Innocent G, Bakshi, Siddharth, Barlow, Samantha L, Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin WA, Clark, Jordan J, Clarke, Emily A, Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis WS, Foster, Terry, Garcia-Dorival, Isabel, Greenhalf, William, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L, Jones, Christopher B, Jones, Trevor R, Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A, Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S, Middleton, Joanna, Mitchell, Joyce, Moore, Shona C, Murphy, Ellen G, Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E, Shears, Rebecca K, Small, Benjamin, Subramaniam, Krishanthi S, Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, Tonder, Libby van, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Carracedo, Alejandra Doce, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Brealey, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B, Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, Otahal, Igor, Pais, Mark, Panchatsharam, Selva, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Pooni, Jagtur, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Wilson, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G, Workman, Andrew, Yates, Bryan, and Young, Peter

Abstract

Studies of patients admitted to hospital with COVID-19 have found varying mortality outcomes associated with underlying respiratory conditions and inhaled corticosteroid use. Using data from a national, multicentre, prospective cohort, we aimed to characterise people with COVID-19 admitted to hospital with underlying respiratory disease, assess the level of care received, measure in-hospital mortality, and examine the effect of inhaled corticosteroid use.

Published
2021
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26. Changes in in-hospital mortality in the first wave of COVID-19: a multicentre prospective observational cohort study using the WHO Clinical Characterisation Protocol UK

Author

Docherty, Annemarie B, Mulholland, Rachel H, Lone, Nazir I, Cheyne, Christopher P, De Angelis, Daniela, Diaz-Ordaz, Karla, Donegan, Cara, Drake, Thomas M, Dunning, Jake, Funk, Sebastian, García-Fiñana, Marta, Girvan, Michelle, Hardwick, Hayley E, Harrison, Janet, Ho, Antonia, Hughes, David M, Keogh, Ruth H, Kirwan, Peter D, Leeming, Gary, Nguyen Van-Tam, Jonathan S, Pius, Riinu, Russell, Clark D, Spencer, Rebecca G, Tom, Brian DM, Turtle, Lance, Openshaw, Peter JM, Baillie, J Kenneth, Harrison, Ewen M, Semple, Malcolm G, Baillie, J Kenneth, Semple, Malcolm G, Openshaw, Peter JM, Carson, Gail, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S, Bogaert, Debby, Chand, Meera, Cooke, Graham S, Docherty, Annemarie B, Dunning, Jake, da Silva Filipe, Ana, Fletcher, Tom, Green, Christopher A, Harrison, Ewen M, Hiscox, Julian A, Ho, Antonia YW, Horby, Peter W, Ijaz, Samreen, Khoo, Say, Klenerman, Paul, Law, Andrew, Lim, Wei Shen, Mentzer, Alexander J, Merson, Laura, Meynert, Alison M, Noursadeghi, Mahdad, Moore, Shona C, Palmarini, Massimo, Paxton, William A, Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L, Russell, Clark D, Sancho-Shimizu, Vanessa, Scott, Janet T, de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Tedder, Richard S, Thomson, Emma C, Thompson, AA Roger, Thwaites, Ryan S, Turtle, Lance CW, Gupta, Rishi K, Palmieri, Carlo, Zambon, Maria, Hardwick, Hayley, Donohue, Chloe, Lyons, Ruth, Griffiths, Fiona, Oosthuyzen, Wilna, Norman, Lisa, Pius, Riinu, Drake, Thomas M, Fairfield, Cameron J, Knight, Stephen R, Mclean, Kenneth A, Murphy, Derek, Shaw, Catherine A, Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Clohisey, Sara, Hendry, Ross, Scott-Brown, James, Greenhalf, William, Shaw, Victoria, McDonald, Sarah E, Keating, Seán, Ahmed, Katie A, Armstrong, Jane A, Ashworth, Milton, Asiimwe, Innocent G, Bakshi, Siddharth, Barlow, Samantha L, Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin WA, Clark, Jordan J, Clarke, Emily A, Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis WS, Foster, Terry, Garcia-Dorival, Isabel, Greenhalf, William, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L, Jones, Christopher B, Jones, Trevor R, Khandaker, Shadia, King, Katharine, Kiy, Robyn T, Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A, Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S, Middleton, Joanna, Mitchell, Joyce, Moore, Shona C, Murphy, Ellen G, Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E, Shears, Rebecca K, Small, Benjamin, Subramaniam, Krishanthi S, Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Doce Carracedo, Alejandra, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, Wrobel, Nicola, McCafferty, Sarah, Morrice, Kirstie, MacLean, Alan, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin L, Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Chadwick, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B, Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, O'Shea, Matthew K, Otahal, Igor, Ostermann, Marlies, Pais, Mark, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Singh Pooni, Jagtur, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Sarah, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G, Workman, Andrew, Yates, Bryan, and Young, Peter

Abstract

Mortality rates in hospitalised patients with COVID-19 in the UK appeared to decline during the first wave of the pandemic. We aimed to quantify potential drivers of this change and identify groups of patients who remain at high risk of dying in hospital.

Published
2021
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27. A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity

Author

Liu, Chang, Zhou, Daming, Dijokaite-Guraliuc, Aiste, Supasa, Piyada, Duyvesteyn, Helen M.E., Ginn, Helen M., Selvaraj, Muneeswaran, Mentzer, Alexander J., Das, Raksha, de Silva, Thushan I., Ritter, Thomas G., Plowright, Megan, Newman, Thomas A.H., Stafford, Lizzie, Kronsteiner, Barbara, Temperton, Nigel, Lui, Yuan, Fellermeyer, Martin, Goulder, Philip, Klenerman, Paul, Dunachie, Susanna J., Barton, Michael I., Kutuzov, Mikhail A., Dushek, Omer, Fry, Elizabeth E., Mongkolsapaya, Juthathip, Ren, Jingshan, Stuart, David I., and Screaton, Gavin R.

Abstract

BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility.

Published
2024
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29. James Webb: an optical success story.

Author

Stuart, David

Subjects
SCIENTIFIC apparatus & instruments, OPTICAL elements, OPTICAL telescopes, SPACE telescopes, MIRRORS
Published
2022

31. Development and validation of the ISARIC 4C Deterioration model for adults hospitalised with COVID-19: a prospective cohort study

Author

Gupta, Rishi K, Harrison, Ewen M, Ho, Antonia, Docherty, Annemarie B, Knight, Stephen R, van Smeden, Maarten, Abubakar, Ibrahim, Lipman, Marc, Quartagno, Matteo, Pius, Riinu, Buchan, Iain, Carson, Gail, Drake, Thomas M, Dunning, Jake, Fairfield, Cameron J, Gamble, Carrol, Green, Christopher A, Halpin, Sophie, Hardwick, Hayley E, Holden, Karl A, Horby, Peter W, Jackson, Clare, Mclean, Kenneth A, Merson, Laura, Nguyen-Van-Tam, Jonathan S, Norman, Lisa, Olliaro, Piero L, Pritchard, Mark G, Russell, Clark D, Scott-Brown, James, Shaw, Catherine A, Sheikh, Aziz, Solomon, Tom, Sudlow, Cathie, Swann, Olivia V, Turtle, Lance, Openshaw, Peter J M, Baillie, J Kenneth, Semple, Malcolm G, Noursadeghi, Mahdad, Baillie, J Kenneth, Semple, Malcolm G, Openshaw, Peter JM, Carson, Gail, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S, Bogaert, Debby, Chand, Meera, Cooke, Graham S, Docherty, Annemarie B, Dunning, Jake, Filipe, Ana da Silva, Fletcher, Tom, Green, Christopher A, Harrison, Ewen M, Hiscox, Julian A, Ho, Antonia Ying Wai, Horby, Peter W, Ijaz, Samreen, Khoo, Saye, Klenerman, Paul, Law, Andrew, Lim, Wei Shen, Mentzer, Alexander J, Merson, Laura, Meynert, Alison M, Noursadeghi, Mahdad, Moore, Shona C, Palmarini, Massimo, Paxton, William A, Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L, Russell, Clark D, Sancho-Shimizu, Vanessa, Scott, Janet T, de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Tedder, Richard S, Thomson, Emma C, Thompson, AA Roger, Thwaites, Ryan S, Turtle, Lance CW, Zambon, Maria, Hardwick, Hayley, Donohue, Chloe, Lyons, Ruth, Griffiths, Fiona, Oosthuyzen, Wilna, Norman, Lisa, Pius, Riinu, Drake, Tom M, Fairfield, Cameron J, Knight, Stephen, Mclean, Kenneth A, Murphy, Derek, Shaw, Catherine A, Dalton, Jo, Lee, James, Plotkin, Daniel, Girvan, Michelle, Mullaney, Scott, Petersen, Claire, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Clohisey, Sara, Hendry, Ross, Scott-Brown, James, Greenhalf, William, Shaw, Victoria, McDonald, Sarah, Keating, Seán, Ahmed, Katie A., Armstrong, Jane A, Ashworth, Milton, Asiimwe, Innocent G, Bakshi, Siddharth, Barlow, Samantha L, Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin WA, Clark, Jordan J, Clarke, Emily A, Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis WS, Foster, Terry, Garcia-Dorival, Isabel, Greenhalf, Willliam, Gunning, Philip, Hartley, Catherine, Ho, Antonia, Jensen, Rebecca L, Jones, Christopher B, Jones, Trevor R, Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, L, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A, Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S, Middleton, Joanna, Mitchell, Joyce, Moore, Shona C, Murphy, Ellen G, Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E, Shears, Rebecca K, Small, Benjamin, Subramaniam, Krishanthi S, Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Brealey, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B, Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, Otahal, Igor, Pais, Mark, Panchatsharam, Selva, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Pooni, Jagtur Singh, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Wilson, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G, Workman, Andrew, Yates, Bryan, and Young, Peter

Abstract

Prognostic models to predict the risk of clinical deterioration in acute COVID-19 cases are urgently required to inform clinical management decisions.

Published
2021
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33. Analysis of Benzenoid Substitution Patterns in Small Molecule Active Pharmaceutical Ingredients

Author

Nilova, Aleksandra, Campeau, Louis-Charles, Sherer, Edward C., and Stuart, David R.

Abstract

Previous analyses have revealed that benzenoid rings are prevalent scaffolds in active pharmaceutical ingredients (APIs). Here, we analyze the substitution patterns of benzenoid rings in small molecule APIs approved by the FDA through 2019 and show that only a few substitution patterns (1-, 1,2-, 1,4-, and 1,2,4-) prevail, and the distribution has remained relatively constant over time. We postulate the connection between available synthetic methods and the occurrence of a few benzenoid substitution patterns by providing an overview of synthetic methods that elaborate existing substitution patterns and those that create new substitution patterns, including those of the former that are favored by medicinal chemists. Finally, we calculated medicinal chemistry properties of benzenoid containing APIs that are often used by practitioners as design elements, including “druglikeness”, shape, complexity, and similarity/diversity and discuss these properties in the context of synthesis.

Published
2020
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34. Broad and strong memory CD4+and CD8+T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

Author

Peng, Yanchun, Mentzer, Alexander J., Liu, Guihai, Yao, Xuan, Yin, Zixi, Dong, Danning, Dejnirattisai, Wanwisa, Rostron, Timothy, Supasa, Piyada, Liu, Chang, López-Camacho, César, Slon-Campos, Jose, Zhao, Yuguang, Stuart, David I., Paesen, Guido C., Grimes, Jonathan M., Antson, Alfred A., Bayfield, Oliver W., Hawkins, Dorothy E. D. P., Ker, De-Sheng, Wang, Beibei, Turtle, Lance, Subramaniam, Krishanthi, Thomson, Paul, Zhang, Ping, Dold, Christina, Ratcliff, Jeremy, Simmonds, Peter, de Silva, Thushan, Sopp, Paul, Wellington, Dannielle, Rajapaksa, Ushani, Chen, Yi-Ling, Salio, Mariolina, Napolitani, Giorgio, Paes, Wayne, Borrow, Persephone, Kessler, Benedikt M., Fry, Jeremy W., Schwabe, Nikolai F., Semple, Malcolm G., Baillie, J. Kenneth, Moore, Shona C., Openshaw, Peter J. M., Ansari, M. Azim, Dunachie, Susanna, Barnes, Eleanor, Frater, John, Kerr, Georgina, Goulder, Philip, Lockett, Teresa, Levin, Robert, Zhang, Yonghong, Jing, Ronghua, Ho, Ling-Pei, Cornall, Richard J., Conlon, Christopher P., Klenerman, Paul, Screaton, Gavin R., Mongkolsapaya, Juthathip, McMichael, Andrew, Knight, Julian C., Ogg, Graham, and Dong, Tao

Abstract

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+and/or CD8+epitopes, including six immunodominant regions. Six optimized CD8+epitopes were defined, with peptide–MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design.

Published
2020
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35. Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Author

Zhou, Daming, Duyvesteyn, Helen M. E., Chen, Cheng-Pin, Huang, Chung-Guei, Chen, Ting-Hua, Shih, Shin-Ru, Lin, Yi-Chun, Cheng, Chien-Yu, Cheng, Shu-Hsing, Huang, Yhu-Chering, Lin, Tzou-Yien, Ma, Che, Huo, Jiandong, Carrique, Loic, Malinauskas, Tomas, Ruza, Reinis R., Shah, Pranav N. M., Tan, Tiong Kit, Rijal, Pramila, Donat, Robert F., Godwin, Kerry, Buttigieg, Karen R., Tree, Julia A., Radecke, Julika, Paterson, Neil G., Supasa, Piyada, Mongkolsapaya, Juthathip, Screaton, Gavin R., Carroll, Miles W., Gilbert-Jaramillo, Javier, Knight, Michael L., James, William, Owens, Raymond J., Naismith, James H., Townsend, Alain R., Fry, Elizabeth E., Zhao, Yuguang, Ren, Jingshan, Stuart, David I., and Huang, Kuan-Ying A.

Abstract

The COVID-19 pandemic has had an unprecedented health and economic impact and there are currently no approved therapies. We have isolated an antibody, EY6A, from an individual convalescing from COVID-19 and have shown that it neutralizes SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KDof 2 nM), and a 2.6-Å-resolution crystal structure of an RBD–EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues within this footprint are key to stabilizing the pre-fusion spike. Cryo-EM analyses of the pre-fusion spike incubated with EY6A Fab reveal a complex of the intact spike trimer with three Fabs bound and two further multimeric forms comprising the destabilized spike attached to Fab. EY6A binds what is probably a major neutralizing epitope, making it a candidate therapeutic for COVID-19.

Published
2020
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36. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2

Author

Huo, Jiandong, Le Bas, Audrey, Ruza, Reinis R., Duyvesteyn, Helen M. E., Mikolajek, Halina, Malinauskas, Tomas, Tan, Tiong Kit, Rijal, Pramila, Dumoux, Maud, Ward, Philip N., Ren, Jingshan, Zhou, Daming, Harrison, Peter J., Weckener, Miriam, Clare, Daniel K., Vogirala, Vinod K., Radecke, Julika, Moynié, Lucile, Zhao, Yuguang, Gilbert-Jaramillo, Javier, Knight, Michael L., Tree, Julia A., Buttigieg, Karen R., Coombes, Naomi, Elmore, Michael J., Carroll, Miles W., Carrique, Loic, Shah, Pranav N. M., James, William, Townsend, Alain R., Stuart, David I., Owens, Raymond J., and Naismith, James H.

Abstract

The SARS-CoV-2 virus is more transmissible than previous coronaviruses and causes a more serious illness than influenza. The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (KDof 39 and 12?nM, respectively) and block its interaction with ACE2. Single-particle cryo-EM revealed that both nanobodies bind to all three RBDs in the spike trimer. Crystal structures of each nanobody–RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD–ACE2 interaction. Nanobody-Fc fusions showed neutralizing activity against SARS-CoV-2 (4–6?nM for H11-H4, 18?nM for H11-D4) and additive neutralization with the SARS-CoV-1/2 antibody CR3022.

Published
2020
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40. Target Identification and Mode of Action of Four Chemically Divergent Drugs against Ebolavirus Infection

Author

Ren, Jingshan, Zhao, Yuguang, Fry, Elizabeth E., and Stuart, David I.

Abstract

Here, we show that four chemically divergent approved drugs reported to inhibit Ebolavirus infection, benztropine, bepridil, paroxetine and sertraline, directly interact with the Ebolavirus glycoprotein. Binding of these drugs destabilizes the protein, suggesting that this may be the mechanism of inhibition, as reported for the anticancer drug toremifene and the painkiller ibuprofen, which bind in the same large cavity on the glycoprotein. Crystal structures show that the position of binding and the mode of interaction within the pocket vary significantly between these compounds. The binding constants (Kd) determined by thermal shift assay correlate with the protein–inhibitor interactions as well as with the antiviral activities determined by virus cell entry assays, supporting the hypothesis that these drugs inhibit viral entry by binding the glycoprotein and destabilizing the prefusion conformation. Details of the protein–inhibitor interactions of these complexes and their relation with binding affinity may facilitate the design of more potent inhibitors.

Published
2024
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43. Anion Metathesis of Diaryliodonium Tosylate Salts with a Solid-Phase Column Constructed from Readily Available Laboratory Consumables

Author

Gallagher, Rory T., Seidl, Thomas L., Bader, Joshua, Orella, Charles, Vickery, Thomas, and Stuart, David R.

Abstract

Herein, we describe the discovery and development of a method to exchange the counteranion component of diaryliodonium salts, which is a critical step for their use in chemical synthesis. The method involves a reusable and readily available solid-phase column assembled from common laboratory consumables. This process avoids challenging product separation associated with other methods for anion metathesis of diaryliodonium salts, and selected examples demonstrate the scope of the method. Hazard analysis (differential scanning calorimetry) on all salts used in this study revealed exotherm initiation temperature in the range of 139–199 °C and exotherm magnitude of 60–845 J/g for a single peak.

Published
2019
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44. Multiple liquid crystalline geometries of highly compacted nucleic acid in a dsRNA virus

Author

Ilca, Serban L., Sun, Xiaoyu, El Omari, Kamel, Kotecha, Abhay, de Haas, Felix, DiMaio, Frank, Grimes, Jonathan M., Stuart, David I., Poranen, Minna M., and Huiskonen, Juha T.

Abstract

Characterizing the genome of mature virions is pivotal to understanding the highly dynamic processes of virus assembly and infection. Owing to the different cellular fates of DNA and RNA, the life cycles of double-stranded (ds)DNA and dsRNA viruses are dissimilar. In terms of nucleic acid packing, dsDNA viruses, which lack genome segmentation and intra-capsid transcriptional machinery, predominantly display single-spooled genome organizations1–8. Because the release of dsRNA into the cytoplasm triggers host defence mechanisms9, dsRNA viruses retain their genomes within a core particle that contains the enzymes required for RNA replication and transcription10–12. The genomes of dsRNA viruses vary greatly in the degree of segmentation. In members of the Reoviridaefamily, genomes consist of 10–12 segments and exhibit a non-spooled arrangement mediated by RNA-dependent RNA polymerases11–14. However, whether this arrangement is a general feature of dsRNA viruses remains unknown. Here, using cryo-electron microscopy to resolve the dsRNA genome structure of the tri-segmented bacteriophage ɸ6 of the Cystoviridaefamily, we show that dsRNA viruses can adopt a dsDNA-like single-spooled genome organization. We find that in this group of viruses, RNA-dependent RNA polymerases do not direct genome ordering, and the dsRNA can adopt multiple conformations. We build a model that encompasses 90% of the genome, and use this to quantify variation in the packing density and to characterize the different liquid crystalline geometries that are exhibited by the tightly compacted nucleic acid. Our results demonstrate that the canonical model for the packing of dsDNA can be extended to dsRNA viruses.

Published
2019
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45. Structure-Based in Silico Screening Identifies a Potent Ebolavirus Inhibitor from a Traditional Chinese Medicine Library

Author

Shaikh, Faraz, Zhao, Yuguang, Alvarez, Luis, Iliopoulou, Maria, Lohans, Christopher, Schofield, Christopher J., Padilla-Parra, Sergi, Siu, Shirley W. I., Fry, Elizabeth E., Ren, Jingshan, and Stuart, David I.

Abstract

Potent Ebolavirus (EBOV) inhibitors will help to curtail outbreaks such as that which occurred in 2014–16 in West Africa. EBOV has on its surface a single glycoprotein (GP) critical for viral entry and membrane fusion. Recent high-resolution complexes of EBOV GP with a variety of approved drugs revealed that binding to a common cavity prevented fusion of the virus and endosomal membranes, inhibiting virus infection. We performed docking experiments, screening a database of natural compounds to identify those likely to bind at this site. Using both inhibition assays of HIV-1-derived pseudovirus cell entry and structural analyses of the complexes of the compounds with GP, we show here that two of these compounds attach in the common binding cavity, out of eight tested. In both cases, two molecules bind in the cavity. The two compounds are chemically similar, but the tighter binder has an additional chlorine atom that forms good halogen bonds to the protein and achieves an IC50of 50 nM, making it the most potent GP-binding EBOV inhibitor yet identified, validating our screening approach for the discovery of novel antiviral compounds.

Published
2019
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46. Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins

Author

Elegheert, Jonathan, Behiels, Ester, Bishop, Benjamin, Scott, Suzanne, Woolley, Rachel E., Griffiths, Samuel C., Byrne, Eamon F. X., Chang, Veronica T., Stuart, David I., Jones, E. Yvonne, Siebold, Christian, and Aricescu, A. Radu

Abstract

Structural, biochemical and biophysical studies of eukaryotic soluble and membrane proteins require their production in milligram quantities. Although large-scale protein expression strategies based on transient or stable transfection of mammalian cells are well established, they are associated with high consumable costs, limited transfection efficiency or long and tedious selection of clonal cell lines. Lentiviral transduction is an efficient method for the delivery of transgenes to mammalian cells and unifies the ease of use and speed of transient transfection with the robust expression of stable cell lines. In this protocol, we describe the design and step-by-step application of a lentiviral plasmid suite, termed pHR-CMV-TetO2, for the constitutive or inducible large-scale production of soluble and membrane proteins in HEK293 cell lines. Optional features include bicistronic co-expression of fluorescent marker proteins for enrichment of co-transduced cells using cell sorting and of biotin ligase for in vivo biotinylation. We demonstrate the efficacy of the method for a set of soluble proteins and for the G-protein-coupled receptor (GPCR) Smoothened (SMO). We further compare this method with baculovirus transduction of mammalian cells (BacMam), using the type-A γ-aminobutyric acid receptor (GABAAR) β3 homopentamer as a test case. The protocols described here are optimized for simplicity, speed and affordability; lead to a stable polyclonal cell line and milligram-scale amounts of protein in 3–4 weeks; and routinely achieve an approximately three- to tenfold improvement in protein production yield per cell as compared to transient transduction or transfection.

Published
2018
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47. Broadly neutralizing antibodies against COVID-19.

Author

Zhou, Daming, Ren, Jingshan, Fry, Elizabeth E, and Stuart, David I

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 has led to hundreds of millions of infections and millions of deaths, however, human monoclonal antibodies (mAbs) can be an effective treatment. Since SARS-CoV-2 emerged, a variety of strains have acquired increasing numbers of mutations to gain increased transmissibility and escape from the immune response. Most reported neutralizing human mAbs, including all approved therapeutic ones, have been knocked down or out by these mutations. Broadly neutralizing mAbs are therefore of great value, to treat current and possible future variants. Here, we review four types of neutralizing mAbs against the spike protein with broad potency against previously and currently circulating variants. These mAbs target the receptor-binding domain, the subdomain 1, the stem helix, or the fusion peptide. Understanding how these mAbs retain potency in the face of mutational change could guide future development of therapeutic antibodies and vaccines. [ABSTRACT FROM AUTHOR]

Published
2023
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48. A multi-country analysis of COVID-19 hospitalizations by vaccination status

Author

Gonçalves, Bronner P., Jassat, Waasila, Baruch, Joaquín, Hashmi, Madiha, Rojek, Amanda, Dasgupta, Abhishek, Martin-Loeches, Ignacio, Reyes, Luis Felipe, Piubelli, Chiara, Citarella, Barbara Wanjiru, Kartsonaki, Christiana, Lefèvre, Benjamin, López Revilla, José W., Lunn, Miles, Harrison, Ewen M., Kraemer, Moritz U.G., Shrapnel, Sally, Horby, Peter, Bisoffi, Zeno, Olliaro, Piero L., Merson, Laura, Abdukahil, Sheryl Ann, Jabal, Kamal Abu, Salah, Nashat Abu, Airlangga, Eka, Hssain, Ali Ait, Akwani, Chika, Al Qasim, Eman, Alberti, Angela, Aldabbourosama, Osama, Alessi, Marta, Alex, Beatrice, Al-Fares, Abdulrahman, Aliudin, Jeffrey, Alkahlout, Mohammed, Almasri, Lana, Al-Saba’a, Yousef, Alves, Rita, Cabrita, Joana Alves, Amaral, Maria, Ampaw, Phoebe, Anchan, Aditya John, Angheben, Andrea, Arabi, Yaseen, Arcadipane, Antonio, Archambault, Patrick, Arenz, Lukas, Arora, Rakesh, Ashley, Elizabeth A., Atique, Anika, Atlowly, Moad, Bach, Benjamin, Baillie, John Kenneth, Baird, J. Kevin, Balan, Valeria, Barbalho, Renata, Barbosa, Nicholas Yuri, Barclay, Wendy S., Barnikel, Michaela, Beer, Netta, Begum, Husna, Bellemare, David, Beltrame, Anna, Bertoli, Giulia, Bianco, Claudia, Humaid, Felwa Bin, Bitton, Jonathan, Blier, Catherine, Bogaert, Debby, Borges, Diogo, Bouhmani, Dounia, Bounphiengsy, Thipsavanh, Bountthasavong, Latsaniphone, Klerk, Bianca Boxma-de, Monteiro, Filipa Brás, Brazzi, Luca, Buchtele, Nina, Buonsenso, Danilo, Burrell, Aidan, Bustos, Ingrid G., Cabrita, Joana, Caceres, Eder, Garcês, Rui Caetano, Campisi, Josie, Canepa, Cecilia, Caoili, Janice, Cardellino, Chiara Simona, Cardoso, Filipa, Cardoso, Filipe, Cardoso, Sofia, Carney, Gayle, Carrier, François Martin, Carson, Gail, Cascão, Mariana, Casimiro, José, Castañeda, Silvia, Castanheira, Nidyanara, Cattaneo, Paolo, Cavalin, Roberta, Cavayas, Alexandros, Cevik, Muge, Chaleunphon, Bounthavy, Chan, Adrienne, Chand, Meera, Chen, Anjellica, Cheng, Matthew Pellan, Chommanam, Danoy, Chow, Yock Ping, Christy, Nathaniel, Claure-Del Granado, Rolando, Clohisey, Sara, Codan, Cassidy, Connor, Marie, Cooke, Graham S., Copland, Mary, Corley, Amanda, Cortegiani, Andrea, Crowl, Gloria, Cruz, Claudina, Csete, Marc, Custodio, Paula, da Silva Filipe, Ana, Dagens, Andrew, Daley, Peter, Dalloul, Zaina, Dalton, Heidi, Dalton, Jo, Damas, Juliana, Daneman, Nick, Dankwa, Emmanuelle A., Dantas, Jorge, D'Aragon, Frédérick, De Rose, Cristina, de Silva, Thushan, Dechert, William, Denis, Emmanuelle, Dishon, Yael, Dhangar, k, Docherty, Annemarie B., Donnelly, Christl A., Donohue, Chloe, Douangdala, Phouvieng, Douglas, James Joshua, Downer, Triona, Downing, Mark, Drake, Thomas, Dryden, Murray, Dubot-Pérès, Audrey, Dudman, Susanne, Dunning, Jake, Duplaix, Mathilde, Durham, Lucian, Dyrhol-Riise, Anne Margarita, Edelstein, Michael, Escher, Martina, Esperatti, Mariano, Santo, Catarina Espírito, Estevão, João, Faheem, Amna, Fairfield, Cameron J., Faria, Pedro, Farshait, Nataly, Fernandes, Jorge, Fernandes, Marília Andreia, Ferrão, Joana, Ferraz, Mário, Ferreira, Bernardo, Figueiredo-Mello, Claudia, Fletcher, Tom, Flynn, Brigid, Fontela, Patricia, Forsyth, Simon, Foti, Giuseppe, Fowler, Robert A., Franch-Llasat, Diego, Fraser, Christophe, Fraser, John F., Ribeiro, Ana Freitas, Friedrich, Caren, Fuentes, Nora, G, Argin, Skeie, Linda Gail, Gamble, Carrol, Garcês, Rui, Garcia-Diaz, Julia, Garcia-Gallo, Esteban, Gavin, Aisling, Germano, Nuno, Ghadimi, Moji, Ghisulal, Praveen Kumar, Giani, Marco, Gibson, Jess, Girvan, Michelle, Goco, Geraldine, Gómez-Junyent, Joan, Grable, Margarite, Green, Christopher A., Greenhalf, William, Griffiths, Fiona, Gruner, Heidi, Gu, Yusing, Guerguerian, Anne-Marie, Guerreiro, Daniela, Haber, Daniel, Habraken, Hannah, Hafez, Wael, Hall, Matthew, Halpin, Sophie, Hamdan, Shaher, Hamers, Raph L., Hamza, Summer, Hardwick, Hayley, Harrison, Janet, Hartman, Alan, Heggelund, Lars, Hendry, Ross, Hennessy, Martina, Hesstvedt, Liv, Higgins, Dawn, Higgins, Rupert, Hinton, Samuel, Ho, Antonia, Holter, Jan Cato, Horcajada, Juan Pablo, Ming-Yang Hsu, Jimmy, Hurd, Abby, Ijaz, Samreen, Illana, Carlos Cañada, Inácio, Hugo, Ippolito, Mariachiara, Isidoro, Tiago, Jaber, Hamza, Jackson, Clare, Jaworsky, Denise, Jenum, Synne, Jouvet, Philippe, Kalicinska, Alina, Kandel, Chris, Katz, Kevin, Kaur, Aasmine, Keating, Seán, Kelly, Andrea, Kelly, Sadie, Kennon, Kalynn, Keomany, Sommay, Khalid, Imrana, Kho, Michelle E., Khoo, Saye, Kiiza, Peter, Granerud, Beathe Kiland, Kildal, Anders Benjamin, Klenerman, Paul, Bekken, Gry Kloumann, Knight, Stephen R., Korten, Volkan, Kosgei, Caroline, Kumar, Deepali, Kutsogiannis, Demetrios, Lamontagne, François, Lanza, Marina, Law, Andrew, Law, Andy, Lawrence, Teresa, Lee, James, Lee, Jennifer, Lee, Todd C., Leeming, Gary, Letizia, Andrew, Bassi, Gianluigi Li, Liang, Janet, Lim, Wei Shen, Lind, Andreas, Lissauer, Samantha, Lopes, Diogo, Lyons, Ruth, Machado, Sara, Majeed, Nimisha Abdul, Manetta, Frank, Sant`Ana Malaque, Ceila Maria, Marquis, Catherine, Marsh, Laura, Marshall, John, Martín-Quiros, Alejandro, Martins, Ana, Rego, Caroline Martins, Martucci, Gennaro, Maslove, David, Matthew, Christina, Mayxay, Mayfong, McArthur, Colin, McCarthy, Anne, McConnochie, Rachael, McDonald, Sarah E., McGeer, Allison, McKay, Chris, McLean, Kenneth A., Menon, Kusum, Mentzer, Alexander J., Mesquita, António, Meyer, Dan, Meynert, Alison M., Mihelis, Efstathia, Monteiro, Agostinho, Montrucchio, Giorgia, Moore, Sarah, Moore, Shona C., Cely, Lina Morales, Moro, Lucia, Morton, Ben, Mudara, Caroline, Muhaisen, Mo’nes, Müller, Fredrik, Müller, Karl Erik, Munshi, Laveena, Murthy, Srinivas, Mustafa, Dana, Nagpal, Dave, Narasimhan, Mangala, Nasa, Prashant, Nelder, Matthew, Neumann, Emily, Ng, Pauline Yeung, Nichol, Alistair D., Norman, Lisa, Notari, Alessandra, Noursadeghi, Mahdad, Nusantara, Dwi Utomo, Occhipinti, Giovanna, O'Hearn, Katie, Oliveira, Larissa, Ong, David S.Y., Oosthuyzen, Wilna, Openshaw, Peter, Palmarini, Massimo, Panarello, Giovanna, Panda, Prasan Kumar, Parke, Rachael, Patricio, Patricia, Patterson, Lisa, Paul, Mical, Paulos, Jorge, Paxton, William A., Pejkovska, Mare, Pereira, Rui, Petrovic, Michele, Pettersen, Frank Olav, Pharand, Scott, Phonemixay, Ooyanong, Phoutthavong, Soulichanya, de Piero, Maria, Pimentel, Carlos, Pires, Catarina, Pitaloka, Ayodhia, Pius, Riinu, Poli, Sergio, Pollakis, Georgios, Post, Andra-Maris, Póvoas, Diana, Powis, Jeff, Praphasiri, Viladeth, Pritchard, Mark G., Semedi, Bambang Pujo, Purcell, Gregory, Quesada, Luisa, Quist-Paulsen, Else, Rafael, Aldo, Rahardjani, Mutia, Ramalho, José, Rangappa, Rajavardhan, Rätsep, Indrek, Reeve, Brenda, Reikvam, Dag Henrik, Ren, Hongru, Rewa, Oleksa, Ricchiuto, Antonia, Rishu, Asgar, Rivera Nuñez, Maria Angelica, Roberts, Stephanie, Robertson, David L., Roche-Campo, Ferran, Rodari, Paola, Roessler, Bernhard, Rossanese, Andrea, Rossetti, Matteo, Russell, Clark D., Holten, Aleksander Rygh, Saba, Isabela, Sadat, Musharaf, Sahraei, Valla, Salazar, Leonardo, Sales, Gabriele, Sanchez, Emely, Sancho-Shimizu, Vanessa, Sandhu, Gyan, Sandulescu, Oana, Santos, Marlene, Sarfo-Mensah, Shirley, Sarmiento, Iam Claire E., Saviciute, Egle, Schaffer, Justin, Schwameis, Michael, Schwartz, Gary, Scott, Janet T., Scott-Brown, James, Semple, Malcolm G., Sequeira, Tânia, Shadowitz, Ellen, Shankar, Anuraj, Shaw, Catherine A., Shaw, Victoria, Mohan Shetty, Dr. Rajesh, Sibounheuang, Bountoy, Sigfrid, Louise, Sillaots, Piret, Sin, Wai Ching, Sinatti, Dario, Singh, Mahendra, Skogen, Vegard, Smith, Sue, Solomon, Joshua, Solomon, Tom, Song, Rima, Spinuzza, Elisabetta, Sriskandan, Shiranee, Staudinger, Thomas, Stecher, Stephanie-Susanne, Steinsvik, Trude, Stiksrud, Birgitte, Streinu-Cercel, Adrian, Streinu-Cercel, Anca, Stuart, David, Subekti, Decy, Suen, Jacky Y., Sultana, Asfia, Summers, Charlotte, Suwarti, Atie, Sztajnbok, Jaques, Tabrizi, Shirin, Taleb, Sara, Tedder, Richard S., Teixeira, João, Tessier-Grenier, Hubert, Thompson, Shaun, Thomson, Emma C., Thorpe, Mathew, Thwaites, Ryan S., Tonby, Kristian, Torre, Marta, Torres Santos-Olmo, Rosario Maria, Turgeon, Alexis F., Turtle, Lance C.W., Tveita, Anders, Twardowski, Pawel, Ullrich, Roman, Uyeki, Timothy M., Valentini, Piero, Val-Flores, Luís, Varrone, Michael, Vidal, José Ernesto, Vieira, César, Villanueva, Joy Ann, Villar, Judit, Villoldo, Andrea, Vitiello, Chiara, Vongsouvath, Manivanh, Wainstein, Marina, Webb, Steve, Wei, Jia, Wesselius, Sanne, Wham, Murray, White, Nicole, Willems, Sue, Williams, Bailey, Williams, Virginie, Wils, Evert-Jan, Wittman, Jessica, Yerkovich, Stephanie, Yiaye, Touxiong, Zahran, Maram, and Zambon, Maria

Abstract

Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes.

Published
2023
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50. The influence of online posting dates on the bibliometric indicators of scientific articles.

Author

Echeverría, Mercedes, Stuart, David, and Cordón-García, José-Antonio

Abstract

Copyright of Revista Española de Documentación Científica is the property of Consejo Superior de Investigaciones Cientificas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2017
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