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SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity.
Nat Commun. 2020 11 26; 11(1):6013.NC

Abstract

SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of the mutated S protein (SG614) with the original (SD614). We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those with SD614. This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. Similar results are obtained with virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion.

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Authors+Show Affiliations

Zhang L
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Jackson CB
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Mou H
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Ojha A
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Peng H
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Quinlan BD
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Rangarajan ES
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Pan A
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Vanderheiden A
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA. Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. Yerkes National Primate Research Center, Atlanta, GA, USA. Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, USA.
Suthar MS
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA. Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA. Yerkes National Primate Research Center, Atlanta, GA, USA. Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, USA.
Li W
National Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
Izard T
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL, USA.
Rader C
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA.
Farzan M
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA. mfarzan@scripps.edu.
Choe H
Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, USA. hchoe@scripps.edu.

MeSH

Amino Acid SubstitutionAngiotensin-Converting Enzyme 2COVID-19HEK293 CellsHumansMutationPandemicsSARS-CoV-2Spike Glycoprotein, CoronavirusVirionVirus AssemblyVirus Internalization

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

33243994

Citation

Zhang, Lizhou, et al. "SARS-CoV-2 Spike-protein D614G Mutation Increases Virion Spike Density and Infectivity." Nature Communications, vol. 11, no. 1, 2020, p. 6013.
Zhang L, Jackson CB, Mou H, et al. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat Commun. 2020;11(1):6013.
Zhang, L., Jackson, C. B., Mou, H., Ojha, A., Peng, H., Quinlan, B. D., Rangarajan, E. S., Pan, A., Vanderheiden, A., Suthar, M. S., Li, W., Izard, T., Rader, C., Farzan, M., & Choe, H. (2020). SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nature Communications, 11(1), 6013. https://doi.org/10.1038/s41467-020-19808-4
Zhang L, et al. SARS-CoV-2 Spike-protein D614G Mutation Increases Virion Spike Density and Infectivity. Nat Commun. 2020 11 26;11(1):6013. PubMed PMID: 33243994.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. AU - Zhang,Lizhou, AU - Jackson,Cody B, AU - Mou,Huihui, AU - Ojha,Amrita, AU - Peng,Haiyong, AU - Quinlan,Brian D, AU - Rangarajan,Erumbi S, AU - Pan,Andi, AU - Vanderheiden,Abigail, AU - Suthar,Mehul S, AU - Li,Wenhui, AU - Izard,Tina, AU - Rader,Christoph, AU - Farzan,Michael, AU - Choe,Hyeryun, Y1 - 2020/11/26/ PY - 2020/09/23/received PY - 2020/10/27/accepted PY - 2020/11/27/entrez PY - 2020/11/28/pubmed PY - 2020/12/15/medline SP - 6013 EP - 6013 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - SARS-CoV-2 variants with spike (S)-protein D614G mutations now predominate globally. We therefore compare the properties of the mutated S protein (SG614) with the original (SD614). We report here pseudoviruses carrying SG614 enter ACE2-expressing cells more efficiently than those with SD614. This increased entry correlates with less S1-domain shedding and higher S-protein incorporation into the virion. Similar results are obtained with virus-like particles produced with SARS-CoV-2 M, N, E, and S proteins. However, D614G does not alter S-protein binding to ACE2 or neutralization sensitivity of pseudoviruses. Thus, D614G may increase infectivity by assembling more functional S protein into the virion. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/33243994/SARS_CoV_2_spike_protein_D614G_mutation_increases_virion_spike_density_and_infectivity_ L2 - https://doi.org/10.1038/s41467-020-19808-4 DB - PRIME DP - Unbound Medicine ER -