Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity

Jie Hu, Chang-Long He, Qing-Zhu Gao, Gui-Ji Zhang, Xiao-Xia Cao, Quan-Xin Long, Hai-Jun Deng, Lu-Yi Huang, Juan Chen, View ORCID ProfileKai Wang, Ni Tang, Ai-Long Huang
doi: https://doi.org/10.1101/2020.06.20.161323
Jie Hu
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chang-Long He
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qing-Zhu Gao
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gui-Ji Zhang
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiao-Xia Cao
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Quan-Xin Long
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hai-Jun Deng
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lu-Yi Huang
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan Chen
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kai Wang
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kai Wang
  • For correspondence: ahuang@cqmu.edu.cn nitang@cqmu.edu.cn wangkai@cqmu.edu.cn
Ni Tang
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ahuang@cqmu.edu.cn nitang@cqmu.edu.cn wangkai@cqmu.edu.cn
Ai-Long Huang
1Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ahuang@cqmu.edu.cn nitang@cqmu.edu.cn wangkai@cqmu.edu.cn
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein that mediates SARS-CoV-2 entry into host cells is a major target for vaccines and therapeutics. Thus, insights into its sequence variations are key to understanding the infection and antigenicity of SARS-CoV-2. A dominant mutational variant at position 614 of the S protein (aspartate to glycine, D614G mutation) was observed in the SARS-CoV-2 genome sequence obtained from the Nextstrain database. Using a pseudovirus-based assay, we identified that S-D614 and S-G614 protein pseudotyped viruses share a common receptor, human angiotensin-converting enzyme 2 (ACE2), which could be blocked by recombinant ACE2 with the fused Fc region of human IgG1. However, S-D614 and S-G614 protein demonstrated functional differences. First, S-G614 protein could be cleaved by serine protease elastase-2 more efficiently. Second, S-G614 pseudovirus infected 293T-ACE2 cells significantly more efficiently than did the S-D614 pseudovirus, especially in the presence of elastase-2. Third, an elastase inhibitor approved for clinical use blocked elastase-enhanced S-G614 pseudovirus infection. Moreover, 93% (65/70) convalescent sera from patients with COVID-19 could neutralize both S-D614 and S-G614 pseudoviruses with comparable efficiencies, but about 7% (5/70) convalescent sera showed reduced neutralizing activity against the S-G614 pseudovirus. These findings have important implications for SARS-CoV-2 transmission and immune interventions.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Figure 1 updated to give structural implications of the spike D614G change. Figure 3 updated to clarify the role of elastase-2. Figure 4 and 5 revised.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted July 06, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity
Jie Hu, Chang-Long He, Qing-Zhu Gao, Gui-Ji Zhang, Xiao-Xia Cao, Quan-Xin Long, Hai-Jun Deng, Lu-Yi Huang, Juan Chen, Kai Wang, Ni Tang, Ai-Long Huang
bioRxiv 2020.06.20.161323; doi: https://doi.org/10.1101/2020.06.20.161323
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity
Jie Hu, Chang-Long He, Qing-Zhu Gao, Gui-Ji Zhang, Xiao-Xia Cao, Quan-Xin Long, Hai-Jun Deng, Lu-Yi Huang, Juan Chen, Kai Wang, Ni Tang, Ai-Long Huang
bioRxiv 2020.06.20.161323; doi: https://doi.org/10.1101/2020.06.20.161323

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (2633)
  • Biochemistry (5220)
  • Bioengineering (3643)
  • Bioinformatics (15706)
  • Biophysics (7210)
  • Cancer Biology (5589)
  • Cell Biology (8038)
  • Clinical Trials (138)
  • Developmental Biology (4731)
  • Ecology (7457)
  • Epidemiology (2059)
  • Evolutionary Biology (10518)
  • Genetics (7694)
  • Genomics (10079)
  • Immunology (5144)
  • Microbiology (13819)
  • Molecular Biology (5349)
  • Neuroscience (30568)
  • Paleontology (211)
  • Pathology (870)
  • Pharmacology and Toxicology (1519)
  • Physiology (2233)
  • Plant Biology (4980)
  • Scientific Communication and Education (1036)
  • Synthetic Biology (1379)
  • Systems Biology (4129)
  • Zoology (802)