Cited by 1,558SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesCOVID-19 Clinical Research Studies

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Spike mutation D614G alters SARS-CoV-2 fitness

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Plante, Jessica A., Liu, Yang, Liu, Jianying, Xia, Hongjie, Johnson, Bryan A., Lokugamage, Kumari G., Zhang, Xianwen, Muruato, Antonio E., Zou, Jing, Fontes-Garfias, Camila R., Mirchandani, Divya, Scharton, Dionna, Bilello, John P., Ku, Zhiqiang, An, Zhiqiang, Kalveram, Birte, Freiberg, Alexander N., Menachery, Vineet D., Xie, Xuping, Plante, Kenneth S., Weaver, Scott C., Shi, Pei-Yong·2021·Nature

DOI 10.1038/s41586-020-2895-3PMC PMC8158177

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Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein substitution D614G became dominant during the coronavirus disease 2019 (COVID-19) pandemic 1,2. 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.

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Authors: Plante, J. A., Liu, Y., Liu, J., Xia, H., Johnson, B. A., Lokugamage, K. G., Zhang, X., Muruato, A. E., Zou, J., Fontes-Garfias, C. R., Mirchandani, D., Scharton, D., Bilello, J. P., Ku, Z., An, Z., Kalveram, B., Freiberg, A. N., Menachery, V. D., Xie, X., Plante, K. S., Weaver, S. C., & Shi, P.-Y.
Affiliations: The University of Texas Medical Branch at Galveston (US)
Gilead Sciences (United States) (US)
Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
Corresponding author: Xie, Xuping
Plante, Kenneth S.
Weaver, Scott C.
Shi, Pei-Yong
ORCID: Plante, Jessica A.
Liu, Jianying
Xia, Hongjie
Johnson, Bryan A.
Zhang, Xianwen
Zou, Jing
Fontes-Garfias, Camila R.
Scharton, Dionna
Bilello, John P.
Ku, Zhiqiang
An, Zhiqiang
Freiberg, Alexander N.
Menachery, Vineet D.
Xie, Xuping
Plante, Kenneth S.
Weaver, Scott C.
Shi, Pei-Yong
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2020-10-26
Volume: 592
Issue: 7852
Pages: 116-121
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-020-2895-3
PMC: PMC8158177
OpenAlex: W3093768302
Cited by: 1,558
References: 37
Citations by year: 2026: 37 · 2025: 73 · 2024: 120 · 2023: 174 · 2022: 427 · 2021: 670 · 2020: 55
FWCI: 43.60
Type: journal article
Language: en
Update notices: correction (2021-06-15)
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
PubMed Central (submittedVersion, cc-by-nc-nd)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Amon G. Carter Foundation
John S. Dunn Foundation (AI145617)
University of Texas System
Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation (AI134907)
National Institutes of Health (AG049042, TL1TR001440, AI145617, AI142759, UL1TR001439)
National Institute on Aging (AI142759, AG049042, R00AG049092)
National Institute of Allergy and Infectious Diseases (R43AI145617, AI142759, R24AI120942, R01AI134907, R21AI145400, U01AI151801, U19AI142759, R01AI153602, AI153602, AG049042, AI134907, AI145617, UC7AI094660)
National Center for Advancing Translational Sciences
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords: SARS-CoV-2, viral fitness, viral replication, upper respiratory tract infection, virus transmission, neutralizing antibodies, vaccine efficacy, hamster model, lung epithelial cells, therapeutic antibodies

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