Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy.
Hongjing Gu,Qi Chen,Guan Yang,Lei He,Hang Fan,Yong Qiang Deng,Yanxiao Wang,Yue Teng,Zhongpeng Zhao,Yujun Cui,Li Yuchang,Xiaofeng Li,Jiangfan Li,Na Na Zhang,Xiaolan Yang,Shaolong Chen,Yan Guo,Guangyu Zhao,Xiliang Wang,De Yan Luo,Hui Wang,Xiao Yang,Yan Li,Gencheng Han,Yuxian He,Xiaojun Zhou,Shusheng Geng,Xiaoli Sheng,Shibo Jiang,Shihui Sun,Cheng-Feng Qin,Yusen Zhou +31 more
TLDR
A mouse model in which a SARS-CoV-2 strain was infectious and could cause an inflammatory response and moderate pneumonia is developed, and a panel of adaptive mutations potentially associated with the increased virulence are revealed.Abstract:
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.read more
Citations
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Characteristics of SARS-CoV-2 and COVID-19
TL;DR: The basic virology of SARS-CoV-2 is described, including genomic characteristics and receptor use, highlighting its key difference from previously known coronaviruses.
Journal ArticleDOI
Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.
Nicholas G Davies,Sam Abbott,Rosanna C. Barnard,Christopher I Jarvis,Adam J. Kucharski,James D Munday,Carl A. B. Pearson,Timothy W Russell,Damien C. Tully,Alex D. Washburne,Tom Wenseleers,Amy Gimma,William Waites,Kerry L. M. Wong,Kevin van Zandvoort,Justin D. Silverman,Karla Diaz-Ordaz,Ruth H. Keogh,Rosalind M Eggo,Sebastian Funk,Mark Jit,Katherine E. Atkins,Katherine E. Atkins,W. John Edmunds +23 more
TL;DR: Using a variety of statistical and dynamic modeling approaches, the authors estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants, and a fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases.
Journal ArticleDOI
SARS-CoV-2 vaccines in development.
TL;DR: The development of vaccines against SARS-CoV-2 is reviewed, including an overview of the development process, the different types of vaccine candidate, and data from animal studies as well as phase I and II clinical trials in humans.
Journal ArticleDOI
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
Mechanisms of SARS-CoV-2 entry into cells.
TL;DR: In this article, structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the spike (S) protein with ACE2, engagement of the receptor-binding domain of the S protein with ACS, proteolytic activation of S protein, endocytosis and membrane fusion are provided.
References
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Nicolas Vabret,Graham J. Britton,Conor Gruber,Samarth Hegde,Joel Kim,Maria Kuksin,Rachel Levantovsky,Louise Malle,Alvaro Moreira,Matthew D. Park,Luisanna Pia,Emma Risson,Miriam Saffern,Bérengère Salomé,Myvizhi Esai Selvan,Matthew P. Spindler,Jessica Tan,Verena van der Heide,Jill Gregory,Konstantina Alexandropoulos,Nina Bhardwaj,Brian D. Brown,Benjamin Greenbaum,Zeynep H. Gümüş,Dirk Homann,Amir Horowitz,Alice O. Kamphorst,Maria A. Curotto de Lafaille,Saurabh Mehandru,Miriam Merad,Robert M. Samstein,Manasi Agrawal,Mark Aleynick,Meriem Belabed,Matthew Brown,Maria Casanova-Acebes,Jovani Catalan,Monica Centa,Andrew Charap,Andrew K Chan,Steven T. Chen,Jonathan Chung,Cansu Cimen Bozkus,Evan Cody,Francesca Cossarini,Erica Dalla,Nicolas F. Fernandez,John A. Grout,Dan Fu Ruan,Pauline Hamon,Etienne Humblin,Divya Jha,Julia Kodysh,Andrew Leader,Matthew Lin,Katherine E. Lindblad,Daniel Lozano-Ojalvo,Gabrielle Lubitz,Assaf Magen,Zafar Mahmood,Gustavo Martinez-Delgado,Jaime Mateus-Tique,Elliot Meritt,Chang Moon,Justine Noel,Timothy O'Donnell,Miyo Ota,Tamar Plitt,Venu Pothula,Jamie Redes,Ivan Reyes Torres,Mark P. Roberto,Alfonso R. Sanchez-Paulete,Joan Shang,Alessandra Soares Schanoski,Maria Suprun,Michelle Tran,Natalie Vaninov,C. Matthias Wilk,Julio A. Aguirre-Ghiso,Dusan Bogunovic,Judy H. Cho,Jeremiah J. Faith,Emilie K. Grasset,Peter S. Heeger,Ephraim Kenigsberg,Florian Krammer,Uri Laserson +87 more
TL;DR: The current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death are summarized.
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