The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera

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Author(s)

Author Name

Raveen Rathnasinghe

Published 4 Projects

Microbiology Infectious Diseases

Sonia Jangra

Published 2 Projects

Infectious Diseases

Anastasija Cupic

Published 1 Project

Infectious Diseases

Carles Martinez-Romero

Published 1 Project

Infectious Diseases

Lubbertus C.F. Mulder

Published 2 Projects

Microbiology Infectious Diseases

Soner Yildiz

Published 1 Project

Infectious Diseases

Angela Choi

Published 1 Project

Infectious Diseases

Ignacio Mena

Published 1 Project

Infectious Diseases

Jana De Vrieze

Published 1 Project

Infectious Diseases

Sadaf Aslam

Published 2 Projects

Infectious Diseases

David A Meekins

Published 1 Project

Infectious Diseases

Chester D. McDowell

Published 1 Project

Infectious Diseases

Velmurugan Balaraman

Published 1 Project

Infectious Diseases

Juergen A. Richt

Published 1 Project

Infectious Diseases

Bruno G De Geest

Published 1 Project

Infectious Diseases

Lisa Miorin

Personalized Virology Initiative

Published 1 Project

Infectious Diseases

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Florian Krammer

Michael Schotsaert

Published 4 Projects

Microbiology Infectious Diseases

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The current COVID-19 (coronavirus disease 19) pandemic, caused by SARS-CoV-2, disproportionally affects the elderly and people with comorbidities like obesity and associated type 2 diabetes mellitus. Small animal models are crucial for the successful development and validation of antiviral vaccines, therapies and to study the role that comorbidities have on the outcome of viral infections. The initially available SARS-CoV-2 isolates require adaptation in order to use the mouse angiotensin converting enzyme 2 (mACE-2) entry receptor and to productively infect the cells of the murine respiratory tract. We have mouse-adapted SARS-CoV-2 by serial passaging a clinical virus isolate in the lungs of mice. We then used low doses of this virus in mouse models for advanced age, diabetes and obesity. Similar to SARS-CoV-2 infection in humans, the outcome of infection with mouse-adapted SARS-CoV-2 resulted in enhanced morbidity in aged and diabetic obese mice. Mutations associated with mouse adaptation occurred in the S, M, N and ORF8 genes. Interestingly, one mutation in the receptor binding domain of the S protein results in the change of an asparagine to tyrosine residue at position 501 (N501Y). This mutation is also present in the newly emerging SARS-CoV-2 variant viruses reported in the U.K. (20B/501Y.V1, B1.1.7 lineage) that is epidemiologically associated with high human to human transmission. We show that human convalescent and post vaccination sera can neutralize the newly emerging N501Y virus variant with similar efficiency as that of the reference USA-WA1/2020 virus, suggesting that current SARS-CoV-2 vaccines will protect against the 20B/501Y.V1 strain.

Infectious Diseases
Infectious Diseases 62 Projects