Spike mutation D614G alters SARS-CoV-2 fitness.
Jessica A. Plante,Yang Liu,Jianying Liu,Hongjie Xia,Bryan A. Johnson,Kumari G. Lokugamage,Xianwen Zhang,Antonio E. Muruato,Jing Zou,Camila R. Fontes-Garfias,Divya Mirchandani,Dionna Scharton,John P. Bilello,Zhiqiang Ku,Zhiqiang An,Birte Kalveram,Alexander N. Freiberg,Vineet D. Menachery,Xuping Xie,Kenneth S. Plante,Scott C. Weaver,Pei Yong Shi +21 more
TLDR
Hamsters infected with SARS-CoV-2 expressing spike D614G (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission.Abstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein substitution D614G became dominant during the coronavirus disease 2019 (COVID-19) pandemic1,2. However, the effect of this variant on viral spread and vaccine efficacy remains to be defined. Here we engineered the spike D614G substitution in the USA-WA1/2020 SARS-CoV-2 strain, and found that it enhances viral replication in human lung epithelial cells and primary human airway tissues by increasing the infectivity and stability of virions. Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Sera from hamsters infected with D614 virus exhibit modestly higher neutralization titres against G614 virus than against D614 virus, suggesting that the mutation is unlikely to reduce the ability of vaccines in clinical trials to protect against COVID-19, and that therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this variant in viral spread and its implications for vaccine efficacy and antibody therapy.read more
Citations
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Detection of a SARS-CoV-2 variant of concern in South Africa.
Houriiyah Tegally,Eduan Wilkinson,Marta Giovanetti,Marta Giovanetti,Arash Iranzadeh,Vagner Fonseca,Vagner Fonseca,Jennifer Giandhari,Deelan Doolabh,Sureshnee Pillay,Emmanuel James San,Nokukhanya Msomi,Koleka Mlisana,Anne von Gottberg,Sibongile Walaza,Mushal Allam,Arshad Ismail,Thabo Mohale,Allison J. Glass,Susan Engelbrecht,Gert U. van Zyl,Wolfgang Preiser,Francesco Petruccione,Alex Sigal,Alex Sigal,Diana Hardie,Gert Marais,Nei yuan Hsiao,Stephen N.J. Korsman,Mary-Ann Davies,Lynn Tyers,Innocent Mudau,Denis York,Caroline Maslo,Dominique Goedhals,Shareef Abrahams,Oluwakemi Laguda-Akingba,Arghavan Alisoltani-Dehkordi,Arghavan Alisoltani-Dehkordi,Adam Godzik,Constantinos Kurt Wibmer,B.T. Sewell,José Lourenço,Luiz Carlos Junior Alcantara,Luiz Carlos Junior Alcantara,Sergei L Kosakovsky Pond,Steven Weaver,Darren P. Martin,Richard J Lessells,Richard J Lessells,Jinal N. Bhiman,Carolyn Williamson,Carolyn Williamson,Tulio de Oliveira,Tulio de Oliveira,Tulio de Oliveira +55 more
TL;DR: A newly arisen lineage of SARS-CoV-2 (designated 501Y.V2) was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province.
Journal ArticleDOI
Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity.
Wilfredo F. Garcia-Beltran,Wilfredo F. Garcia-Beltran,Evan C. Lam,Kerri St. Denis,Adam Nitido,Zeidy H. Garcia,Blake M. Hauser,Jared Feldman,Maia N. Pavlovic,David Gregory,Mark C. Poznansky,Alex Sigal,Alex Sigal,Aaron G. Schmidt,A. John Iafrate,Vivek Naranbhai,Vivek Naranbhai,Alejandro B. Balazs +17 more
TL;DR: In this article, the authors evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2.
Posted ContentDOI
Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa
Houriiyah Tegally,Eduan Wilkinson,Marta Giovanetti,Marta Giovanetti,Arash Iranzadeh,Vagner Fonseca,Vagner Fonseca,Jennifer Giandhari,Deelan Doolabh,Sureshnee Pillay,Emmanuel James San,Nokukhanya Msomi,Koleka Mlisana,Koleka Mlisana,Anne von Gottberg,Anne von Gottberg,Sibongile Walaza,Sibongile Walaza,Mushal Allam,Arshad Ismail,Thabo Mohale,Allison J. Glass,Susan Engelbrecht,Gert U. van Zyl,Wolfgang Preiser,Francesco Petruccione,Alex Sigal,Alex Sigal,Diana Hardie,Gert Marais,Marvin Hsiao,Stephen N.J. Korsman,Mary-Ann Davies,Lynn Tyers,Innocent Mudau,Denis York,Caroline Maslo,Dominique Goedhals,Shareef Abrahams,Oluwakemi Laguda-Akingba,Oluwakemi Laguda-Akingba,Arghavan Alisoltani-Dehkordi,Arghavan Alisoltani-Dehkordi,Adam Godzik,Constantinos Kurt Wibmer,B.T. Sewell,José Lourenço,Luiz Carlos Junior Alcantara,Luiz Carlos Junior Alcantara,Sergei L Kosakovsky Pond,Steven Weaver,Darren P. Martin,Richard J Lessells,Richard J Lessells,Jinal N. Bhiman,Jinal N. Bhiman,Carolyn Williamson,Carolyn Williamson,Tulio de Oliveira,Tulio de Oliveira,Tulio de Oliveira +60 more
TL;DR: In this paper, the authors describe a new SARS-CoV-2 lineage (501Y.V2) characterised by eight lineage-defining mutations in the spike protein, including three at important residues in the receptor-binding domain (K417N, E484K and N501Y).
Journal ArticleDOI
Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.
Erik M. Volz,Verity Hill,John T. McCrone,Anna Price,David Jorgensen,Áine O'Toole,Joel Southgate,Robert Johnson,Ben Jackson,Fabrícia F. Nascimento,Sara Rey,Samuel M. Nicholls,Rachel M. Colquhoun,Ana da Silva Filipe,James G Shepherd,David J Pascall,Rajiv Shah,Natasha Jesudason,Kathy Li,Ruth F. Jarrett,Nicole Pacchiarini,Matthew J. Bull,Lily Geidelberg,Igor Siveroni,Ian Goodfellow,Nicholas J. Loman,Oliver G. Pybus,David Robertson,E. Thomson,Andrew Rambaut,Thomas R. Connor +30 more
TL;DR: Investigation of the hypothesis for positive selection of Spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage.
Journal ArticleDOI
SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies.
Markus Hoffmann,Markus Hoffmann,Prerna Arora,Prerna Arora,Rüdiger Groß,Alina Seidel,Bojan F. Hörnich,Alexander S. Hahn,Nadine Krüger,Luise Graichen,Heike Hofmann-Winkler,Amy Kempf,Amy Kempf,Martin Sebastian Winkler,Sebastian R. Schulz,Hans-Martin Jäck,Bernd Jahrsdörfer,Bernd Jahrsdörfer,Hubert Schrezenmeier,Hubert Schrezenmeier,Martin Müller,Alexander Kleger,Jan Münch,Stefan Pöhlmann,Stefan Pöhlmann +24 more
TL;DR: In this article, the authors show that SARS-CoV-2/COVID-19 variants B.1.7 (UK), B.351 (South Africa), and P.1 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies.
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Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus.
Bette T. Korber,Will Fischer,Sandrasegaram Gnanakaran,Hyejin Yoon,James Theiler,Werner Abfalterer,Nick Hengartner,Elena E. Giorgi,Tanmoy Bhattacharya,Brian T. Foley,Kathryn M. Hastie,Matthew Parker,David G Partridge,Cariad Evans,Timothy M. Freeman,Thushan I de Silva,Adrienne Angyal,Rebecca Brown,Laura Carrilero,Luke R. Green,Luke R. Green,Luke R. Green,Danielle C. Groves,Katie Johnson,Alexander J Keeley,Benjamin B Lindsey,Paul J. Parsons,Mohammad Raza,Sarah Rowland-Jones,Nikki Smith,Rachel Tucker,Dennis Wang,Matthew Wyles,Charlene McDanal,Lautaro G. Perez,Haili Tang,Alex Moon-Walker,Alex Moon-Walker,Alex Moon-Walker,Sean P. J. Whelan,Celia C. LaBranche,Erica Ollmann Saphire,David C. Montefiori +42 more
TL;DR: A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic, and it is found that the G614 variant grows to higher titer as pseudotyped virions.
Journal ArticleDOI
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Lisa A. Jackson,Evan J. Anderson,Nadine Rouphael,Paul C. Roberts,Mamodikoe Makhene,Rhea N. Coler,Michele Paine McCullough,James D. Chappell,Mark R. Denison,Laura J. Stevens,Andrea J. Pruijssers,Adrian B. McDermott,Britta Flach,Nicole A. Doria-Rose,Kizzmekia S. Corbett,Kaitlyn M. Morabito,Sijy O’Dell,Stephen D. Schmidt,Phillip A. Swanson,Marcelino Padilla,John R. Mascola,Kathleen M. Neuzil,Hamilton Bennett,Wellington Sun,Etza Peters,Mat Makowski,Jim Albert,Kaitlyn Cross,Wendy Buchanan,Rhonda Pikaart-Tautges,Julie E. Ledgerwood,Barney S. Graham,John H. Beigel +32 more
TL;DR: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified, which support further development of this vaccine.
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Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus.
Bette T. Korber,Will Fischer,Sandrasegaram Gnanakaran,Hyejin Yoon,James Theiler,Werner Abfalterer,Nick Hengartner,Elena E. Giorgi,Tanmoy Bhattacharya,Brian T. Foley,Kathryn M. Hastie,Matthew Parker,David G Partridge,Cariad Evans,Timothy M. Freeman,Thushan I de Silva,Adrienne Angyal,Rebecca Brown,Laura Carrilero,Luke R. Green,Luke R. Green,Luke R. Green,Danielle C. Groves,Katie Johnson,Alexander J Keeley,Benjamin B Lindsey,Paul J. Parsons,Mohammad Raza,Sarah Rowland-Jones,Nikki Smith,Rachel Tucker,Dennis Wang,Matthew Wyles,Charlene McDanal,Lautaro G. Perez,Haili Tang,Alex Moon-Walker,Alex Moon-Walker,Alex Moon-Walker,Sean P. J. Whelan,Celia C. LaBranche,Erica Ollmann Saphire,David C. Montefiori +42 more
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Peng Zhou,Xing-Lou Yang,Xian Guang Wang,Ben Hu,Lei Zhang,Wei Zhang,Hao Rui Si,Yan Zhu,Bei Li,Chao Lin Huang,Hui-Dong Chen,Jing Chen,Yun Luo,Hua Guo,Ren Di Jiang,Meiqin Liu,Ying Chen,Xu Rui Shen,Xi Wang,Xiao Shuang Zheng,Kai Zhao,Quanjiao Chen,Fei Deng,Lin Lin Liu,Bing Yan,Fa Xian Zhan,Yan-Yi Wang,Gengfu Xiao,Zhengli Shi +28 more