Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Daniel Wrapp,Nianshuang Wang,Kizzmekia S. Corbett,Jory A. Goldsmith,Ching-Lin Hsieh,Olubukola M. Abiona,Barney S. Graham,Jason S. McLellan +7 more
TLDR
The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.Abstract:
The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.read more
Citations
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Structural insights into SARS-CoV-2 proteins
Rimanshee Arya,Shweta Kumari,B D Pandey,Hiral Mistry,Subhash C. Bihani,Amit Das,Vishal Prashar,Gagan D. Gupta,Lata Panicker,Mukesh Kumar,Mukesh Kumar +10 more
TL;DR: Important structural features of different SARS-CoV-2 proteins with their function, and their potential as a target for therapeutic interventions are discussed.
Journal ArticleDOI
Updated Approaches against SARS-CoV-2.
TL;DR: This minireview aims to summarize the updated potential approaches against SARS-CoV-2 and emphasizes that further efforts are warranted to develop the safest and most effective approach.
Journal ArticleDOI
Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant.
Jun Zhang,Tianshu Xiao,Tianshu Xiao,Yongfei Cai,Yongfei Cai,Christy L. Lavine,Hanqin Peng,Haisun Zhu,Krishna Anand,Pei Tong,Avneesh Gautam,Avneesh Gautam,Megan L. Mayer,Richard M. Walsh,Sophia Rits-Volloch,Duane R. Wesemann,Duane R. Wesemann,Wei Yang,Michael S. Seaman,Jianming Lu,Bing Chen,Bing Chen +21 more
TL;DR: The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a dominant strain worldwide as discussed by the authors, and the structure, func...
Journal ArticleDOI
A Single-Cell RNA Expression Map of Human Coronavirus Entry Factors
TL;DR: Both pro- and anti-viral factors are highly expressed within the nasal epithelium, with potential age-dependent variation, predicting an important battleground for coronavirus infection.
Journal ArticleDOI
SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway
Brian J. Willett,Joe Grove,Oscar A. MacLean,Craig Wilkie,Giuditta De Lorenzo,Wilhelm Furnon,Diego Cantoni,S. Scott,Nicola S Logan,Shirin Ashraf,M. Manali,Agnieszka M. Szemiel,Vanessa M. Cowton,Elen Vink,Chris Davis,Patawee Asamaphan,Richard J. Orton,P Holland,Vanessa Silva,David J Pascall,Kathryn Puxty,Sharif Shaaban Muhammad Shaaban,Matthew T. G. Holden,Rute Maria Pinto,Kate Templeton,Pablo R. Murcia,Arvind H. Patel,Paul Klenerman,Susanna Dunachie,Eleanor Barnes,Anthony Brown,S Adele,Barbara Kronsteiner,Sam M. Murray,P. Abraham,Alexandra Deeks,M A Ansari,Lance Turtle,Shona C Moore,James Austin,Alex G. Richter,Christopher J A Duncan,Rebecca Payne,Amy Ehrlich Ash,C. J. Koshy,Beatrix Kele,Teresa Cutino-Moguel,Derek Fairley,James McKenna,Tanya Curran,Helen Adams,Christophe Fraser,David Bonsall,Helen R. Fryer,Katrina A. Lythgoe,Laura Hayden Thomson,Tanya Golubchik,Abigail Murray,D. Singleton,Shaun M. Beckwith,A Mantzouratou,Magdalena Barrow,Sarah L. Buchan,Nicola Reynolds,Ben Warne,Joshua Maksimovic,Karla Spellman,Kathryn Mccluggage,M. John,Robert H. Beer,Safiah Afifi,Sian Natasha Morgan,Andrew L. Mack,Angela Marchbank,Anna Price,A.C. Morriss,Catherine Bresner,Christine Kitchen,I. Merrick,Joel Southgate,Martyn F Guest,Owen Bowden Jones,Robert F. Munn,Thomas R. Connor,Tom Whalley,T. Race Workman,William Oliver Fuller,Amita Patel,Bindi Patel,G. Nebbia,Jonathan D. Edgeworth,Luke B Snell,Rahul Batra,Themoula Charalampous,Angela Helen Beckett,Ekaterina Shelest,Samuel Robson,Anthony Underwood,Benjamin Taylor,Corin Yeats,David M. Aanensen,Khalil Abudahab,Mirko Menegazzo,Amelia Joseph,Gemma Clark,Hannah C. Howson-Wells,Louise Berry,Manjinder Khakh,Michelle Lister,T. Boswell,Vicki M. Fleming,Christopher W Holmes,Claire McMurray,Jessica R. Shaw,Julian W. Tang,Karlie Fallon,Minaxshi Odedra,Nicholas J. Willford,Paul W Bird,Thomas Helmer,L.A. Williams,Nicole R. Sheriff,Sharon Campbell,Veena Raviprakash,Vickie L. Blakey,Christopher I. Moore,Fei Sang,Johnny Debebe,Matthew Carlile,Matthew Loose,Nadine Holmes,Victoria Wright,M. Torok,William L Hamilton,Alessandro M Carabelli,Andrew Jermy,Beth Blane,Carol Churcher,Catherine Ludden,Dinesh Aggarwal,Elaine J. Westwick,Ellen Brigid Brooks,Georgina M. McManus,Katerina Galai,Ken R. Smith,Kim Smith,MacGregor Cox,Mireille Fragakis,Patrick Maxwell,Sarah Judges,Sharon J. Peacock,Theresa Feltwell,A. K. Kenyon,Sahar Eldirdiri,Thomas Davis,Joshua F. Taylor,NgeeKeong Tan,Alexander E. Zarebski,Bernardo Gutierrez,Jayna Raghwani,Louis du Plessis,Moritz U. G. Kraemer,Oliver G. Pybus,Sarah François,S. W. Attwood,Tetyana I. Vasylyeva,Aminu S Jahun,Ian Goodfellow,Iliana Georgana,Malte L Pinckert,Myra Hosmillo,Rhys E. Izuagbe,Yasmin Chaudhry,Felicity Ryan,Hannah Louise Lowe,Samuel Rajan Moses,Luke Bedford,James S Cargill,Warwick S. Hughes,J. Moore,Susanne Stonehouse,Divya Shah,Jack Lee,Julianne R Brown,Kathryn A. Harris,Laura Atkinson,Nathaniel Storey,Moira J. Spyer,Flavia Flaviani,Adela Alcolea-Medina,J. Sehmi,John Ramble,Natasha Ohemeng-Kumi,P. Smith,B. Bertolusso,Claire P Thomas,Gabrielle Vernet,Jessica Lynch,Nathan Moore,Nicholas Cortes,Rebecca Williams,Stephen P. Kidd,L. J. Levett,Monika Pusok,Paul Grant,Stuart Kirk,W. J. Chatterton,Li Xu-McCrae,Darren L. Smith,Gregor Young,Matthew Bashton,Katie Kitchman,Kavitha Gajee,K. Eastick,Patrick J. Lillie,Phillipa Burns,William G. Everson,Alison Cox,Alison Holmes,Frances Bolt,James R. Price,Marcus Pond,Paul Randell,Pinglawathee Madona,Siddharth Mookerjee,Erik M. Volz,Lily Geidelberg,Manon Ragonnet-Cronin,Olivia Boyd,Robert Johnson,Cassie F Pope,Adam A. Witney,Irene M. Monahan,Ken Laing,Katherine Smollett,Alan McNally,Joanne Stockton,Joshua Quick,Nicholas J. Loman,Radoslaw Poplawski,Samuel M. Nicholls,Will P. M. Rowe,Anibolina Castigador,Emily Macnaughton,Kate El Bouzidi,Malur Sudhanva,Temi Lampejo,Rocio Martinez Nunez,Cathy Breen,Graciela Sluga,Karen T. Withell,Nicholas W Machin,Ryan George,Shazaad Ahmad,David Pritchard,D. Binns,Nick Wong,Victoria L. James,Cheryl Williams,Christopher J. R. Illingworth,Christopher Jackson,Daniela De Angelis,Afrida Mukaddas,Alice Broos,Ana da Silva Filipe,Daniel Mair,David Robertson,Derek W. Wright,E. Thomson,Igor Starinskij,Ioulia Tsatsani,James Shepherd,Jenna Nichols,Joseph Hughes,Kyriaki Nomikou,Lily Tong,Sreenu B. Vattipally,William T. Harvey,Roy A. Sanderson,S. O’Brien,Steven Rushton,Jon Davis Perkins,Rachel Blacow,Rory Gunson,A. Gallagher,Elizabeth Wastnedge,Martin P McHugh,Rebecca Dewar,Seb Cotton,Lindsay Coupland,R.Suganya and Dr. Shaleesha A. Stanley,Samir Dervisevic,Lewis G. Spurgin,Louise Smith,Clive Graham,D. Padgett,Edward Barton,Garren Scott,Aidan Cross,Mariyam Mirfenderesky,E. Swindells,J Greenaway,Rebecca Denton-Smith,Robyn Turnbull,Giles Idle,Kevin Cole,Amy Louise Hollis,Andrew T. Nelson,C. McCann,Joan H Henderson,M. Crown,Wen Chyin Yew,W Stawski Stanley,Nicholas Duckworth,Phillip Clarke,Sarah Walsh,Tim J. Sloan,Kelly Bicknell,R. L. Impey,Sarah Wyllie,Scott M. Elliott,Sharon Glaysher,Declan Bradley,Nicholas Killough,Tim W. Wyatt,Andrew Bosworth,Barry Vipond,Clare Pearson,Elias Allara,E. E Robinson,Hannah M. Pymont,Husam Osman,Peter C. Muir,Richard Hopes,S. A. Hutchings,Martin D. Curran,Surendra S. Parmar,A Thornton,Angie Lackenby,Chloe Bishop,David F. Bibby,Dave Lee,Eileen Gallagher,Gavin Dabrera,Ian Harrison,Jonathan Hubb,Katherine A. Twohig,Meera Chand,Nicholas Ellaby,Nikos Manesis,R. Myers,Steven Platt,Tamyo Mbisa,Vicki Chalker,Gonzalo Yebra,Stefan Rooke,Alec Birchley,Alexander Adams,A Davies,Amy E. Gaskin,Bree Gatica-Wilcox,Caoimhe McKerr,Catherine Moore,Catryn Williams,Chris Williams,David Heyburn,Elen de Lacy,Ember Hilvers,Fatima Downing,Georgia Pugh,Hannah Jones,Hibo Asad,Jason D. Coombes,Jessica G. Hey,Jessica L. Powell,Joanne Watkins,John Evans,Laia Fina,Laura Gifford,L Gilbert,Lee H. Graham,Malorie Perry,Mari Morgan,Matthew Bull,Nicole Pacchiarini,Noel Craine,Sally Corden,Sara Kumžiene-Summerhayes,Sara Rey,Sarah Taylor,Simon Cottrell,Sophie Jones,Sue Edwards,Tara Annett,Alexander J. Trotter,Alison E. Mather,Alp Aydin,Andrew J. Page,David J. Baker,Ebenezer Foster-Nyarko,Gemma L. Kay,Justin O'Grady,Leonardo de Oliveira Martins,Lizzie Meadows,Nabil-Fareed Alikhan,Sophie J Prosolek,Steven J. Rudder,Thanh Le-Viet,Anna Casey,Liz Ratcliffe,Aditi Singh,Arun Mariappan,Chris L. Baxter,Clara Radulescu,David Simpson,Debra Redman Lavin,Fiona Rogan,Julia Miskelly,Marc Fuchs,Miao Tang,Sílvia F. Carvalho,Stephen Bridgett,Timofey Skvortsov,Zoltán Molnár,Newara Ramadan,Bridget A. Knight,Christopher R. Jones,Cressida Auckland,Helen Morcrette,Jennifer Lee Poyner,Dianne Irish-Tavares,Eric Witele,Jennifer Hart,Tabitha Mahungu,Tanzina Haque,Yann Bourgeois,Christopher Fearn,Kate Cook,Katie F. Loveson,Salman Goudarzi,Cariad Evans,David G Partridge,Katie Johnson,Mehmet Yavus,Mohammad Raza,Craig Mower,Paul Baker,Sarah Essex,Stephen Bonner,Leanne Murray,Louisa K. Watson,Steven P. Liggett,Andrew I. Lawton,Ronan A Lyons,Brendan A I Payne,G Eltringham,Jennifer Collins,Sheila Waugh,Shirelle Burton-Fanning,Yusri Taha,Christopher Jeanes,Andrea N. Gomes,Darren Murray,Maimuna Kimuli,D Dobie,Paula Ashfield,Angus I. Best,Benita Percival,Emma Moles-Garcia,F. Ashford,Jeremy Mirza,L. Crawford,Megan Mayhew,Nicola Cumley,Oliver Megram,Dan Frampton,Judith Heaney,Matthew Byott,C. Houlihan,Charlotte A Williams,Eleni Nastouli,Helen Lowe,John A. Hartley,Judith Breuer,Laurentiu Maftei,Leah Ensell,Marius Cotic,Matteo Mondani,Molly Driscoll,N. Bayzid,Rachel Williams,Sunando Sur Roy,Adhyana I K Mahanama,Buddhini Samaraweera,Eleri Wilson-Davies,Emanuela Pelosi,H.C Umpleby,Helen Wheeler,Jacqui Prieto,Kordo Saeed,Matthew Harvey,Sarah Jeremiah,Siona Silviera,Stephen Aplin,T. Sass,BS Macklin,Dorian Crudgington,Liz Sheridan,Benjamin J. Cogger,Cassandra Malone,Florence Munemo,Hannah Huckson,Jonathan Lewis,Lisa J. Easton,Manasa Mutingwende,Michelle J. Erkiert,Mohammed O. Hassan-Ibrahim,N. Chaloner,Olga Podplomyk,Paul Randell,Roberto Nicodemi,Sarah L. Lowdon,Thomas Somassa,Andrew Beggs,Andrew Hesketh,Colin P. Smith,Giselda Bucca,Christopher Ruis,Claire Cormie,Ellen E. Higginson,Jamie Young,Joana Dias,L. Kermack,Mailis Maes,Ravi Gupta,Sally Forrest,Sophia T. Girgis,Rose K Davidson,Áine O'Toole,Andrew Rambaut,Ben Jackson,Carlos Balcazar,Daniel S. Maloney,Emily Scher,J. McCrone,Katherine A. Williamson,Michael D. Gallagher,Nathan C Medd,Rachel M. Colquhoun,Thomas D. Stanton,Thomas C Williams,Verity Hill,Aaron R. Jeffries,Ben Temperton,Christine Sambles,David J. Studholme,Joanna Warwick-Dugdale,Leigh Jackson,Michelle Michelsen,R. Manley,Stephen L. Michell,Alistair C. Darby,Anita Lucaci,Charlotte Nelson,Claudia Wierzbicki,Edith E. Vamos,Hermione J. Webster,Kathryn A. Jackson,Lucille Rainbow,Margaret Lawrence Hughes,Mark Whitehead,Matthew Gemmell,Miren Iturriza-Gomara,Richard Eccles,Richard Gregory,Sam Haldenby,Steve Paterson,Adrienn Angyal,Alexander J Keeley,Benjamin Foulkes,Benjamin B Lindsey,Dennis Wang,Hailey Hornsby,Luke R. Green,Manoj Baliram Pohare,M. Gallis,Matthew Parker,M. Whiteley,Nikki Smith,P. Wolverson,Peijun Zhang,Samantha Hansford,Sharon N. Hsu,S. Louka,Thushan I de Silva,Timothy M. Freeman,Matilde Mori,Emily J. Park,Jack Hill,Jayasree Dey,Jonathan K. Ball,Joseph G. Chappell,Patrick McClure,Timothy Byaruhanga,A Fanaie,Geraldine Yaze,Rachel A. Hilson,Amy Trebes,Angie Green,David Buck,G. Macintyre-Cockett,John A. Todd,Andrew R. Bassett,Andrew Whitwham,Cordelia Langford,Diana Rajan,Dominic P. Kwiatkowski,J. Harrison,Iraad F. Bronner,Jaime M. Tovar-Corona,Jennifier Liddle,Jillian Durham,Katherine L. Bellis,Kevin Lewis,Louise Aigrain,Nicholas Redshaw,Robert L. Davies,Robin J. Moll,Shane A. McCarthy,Stefanie V Lensing,Steven Leonard,Ben Farr,C. Scott,Charlotte M. Beaver,Cristina V. Ariani,Da Weldon,David Jackson,Emma Betteridge,Gerry Tonkin-Hill,Ian Johnston,Inigo Martincorena,James K. Bonfield,Jeffrey C. Barrett,John Sillitoe,J P Keatley,Karen A. Oliver,Keith James,Lesley Shirley,Liam J. Prestwood,Luke Foulser,Marina Gourtovaia,Matthew J. Dorman,Michael A. Quail,Michael Spencer Chapman,Naomi Park,Rich Livett,Roberto Amato,Sally Kay,Scott Goodwin,Scott Thurston,Shavanthi Rajatileka,Sónia Gonçalves,Stephanie Lo,Theo Sanderson,Alasdair MacLean,Emily Goldstein,Lynne Ferguson,Rachael M. Tomb,Jana Catalan,Neil Jones,John Haughney,Massimo Palmarini,Surajit Ray +672 more
TL;DR: In this article , the authors demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273.529.
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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
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