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

The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13

View ORCID ProfileShufeng Liu, Prabhuanand Selvaraj, Christopher Z. Lien, Wells W. Wu, Chao-Kai Chou, Tony T. Wang
doi: https://doi.org/10.1101/2020.07.20.213280
Shufeng Liu
1Laboratory of Vector-Borne Viral Diseases, Division of Viral Products, Center for Biologics Evaluation, U.S. Food and Drug Administration, Silver Spring, Maryland, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Shufeng Liu
Prabhuanand Selvaraj
1Laboratory of Vector-Borne Viral Diseases, Division of Viral Products, Center for Biologics Evaluation, U.S. Food and Drug Administration, Silver Spring, Maryland, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher Z. Lien
1Laboratory of Vector-Borne Viral Diseases, Division of Viral Products, Center for Biologics Evaluation, U.S. Food and Drug Administration, Silver Spring, Maryland, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wells W. Wu
2Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chao-Kai Chou
2Facility for Biotechnology Resources, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tony T. Wang
1Laboratory of Vector-Borne Viral Diseases, Division of Viral Products, Center for Biologics Evaluation, U.S. Food and Drug Administration, Silver Spring, Maryland, United States of America
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Tony.Wang@fda.hhs.gov
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

Biochemical and structural analyses suggest that SARS-CoV-2 is well-adapted to infecting human and the presence of four residues (PRRA) at the S1/S2 site within the Spike protein may lead to unexpected tissue or host tropism. Here we report that SARS-CoV-2 efficiently utilized ACE2 of 9 species except mouse to infect 293T cells. Similarly, pseudoviruses bearing spike protein derived from either the bat raTG13 or pangolin GX, two closely related animal coronaviruses, utilized ACE2 of a diverse range of animal species to gain entry. Removal of PRRA from SARS-CoV-2 Spike displayed distinct effects on pseudoviral entry into different cell types. Strikingly, insertion of PRRA into the raTG13 Spike selectively abrogated the usage of horseshoe bat and pangolin ACE2 but conferred usage of mouse ACE2 by the relevant pseudovirus to enter cells. Together, our findings identified a previously unrecognized effect of the PRRA insert on SARS-CoV-2 and raTG13 spike proteins.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted July 21, 2020.
Download PDF
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.
The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13
(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
The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13
Shufeng Liu, Prabhuanand Selvaraj, Christopher Z. Lien, Wells W. Wu, Chao-Kai Chou, Tony T. Wang
bioRxiv 2020.07.20.213280; doi: https://doi.org/10.1101/2020.07.20.213280
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
The PRRA insert at the S1/S2 site modulates cellular tropism of SARS-CoV-2 and ACE2 usage by the closely related Bat raTG13
Shufeng Liu, Prabhuanand Selvaraj, Christopher Z. Lien, Wells W. Wu, Chao-Kai Chou, Tony T. Wang
bioRxiv 2020.07.20.213280; doi: https://doi.org/10.1101/2020.07.20.213280

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 (4081)
  • Biochemistry (8754)
  • Bioengineering (6472)
  • Bioinformatics (23330)
  • Biophysics (11728)
  • Cancer Biology (9141)
  • Cell Biology (13234)
  • Clinical Trials (138)
  • Developmental Biology (7405)
  • Ecology (11364)
  • Epidemiology (2066)
  • Evolutionary Biology (15081)
  • Genetics (10394)
  • Genomics (14005)
  • Immunology (9114)
  • Microbiology (22030)
  • Molecular Biology (8774)
  • Neuroscience (47335)
  • Paleontology (350)
  • Pathology (1419)
  • Pharmacology and Toxicology (2480)
  • Physiology (3702)
  • Plant Biology (8044)
  • Scientific Communication and Education (1430)
  • Synthetic Biology (2206)
  • Systems Biology (6013)
  • Zoology (1248)