https://www.nature.com/articles/s41586-021-03312-w Skip to main content Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement Advertisement Nature * View all Nature Research journals * Search * My Account Login * Explore content * Journal information * Publish with us * Sign up for alerts * RSS feed 1. nature 2. articles 3. article SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801 Download PDF * Article * Published: 09 February 2021 This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply. SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801 * Angela Wahl^1,2,3^ na1, * Lisa E. Gralinski^4^ na1, * Claire E. Johnson ORCID: orcid.org/0000-0003-0048-6592^1,2,3, * Wenbo Yao^1,2,3, * Martina Kovarova^1,2,3, * Kenneth H. Dinnon III ORCID: orcid.org/0000-0002-8942-1551^4,5, * Hongwei Liu^6,7, * Victoria J. Madden ORCID: orcid.org/0000-0002-7909-7743^8, * Halina M. Krzystek^6,7, * Chandrav De^1,2,3, * Kristen K. White^8, * Kendra Gully ORCID: orcid.org/0000-0001-5742-2341^4, * Alexandra Schafer^4, * Tanzila Zaman^6,7, * Sarah R. Leist^4, * Paul O. Grant ORCID: orcid.org/0000-0001-6640-6415^6,7, * Gregory R. Bluemling ORCID: orcid.org/0000-0001-9138-7578^9,10, * Alexander A. Kolykhalov^9,10, * Michael G. Natchus^10, * Frederic B. Askin^11, * George Painter^9,10,12, * Edward P. Browne^2,3,5,13, * Corbin D. Jones^6,7, * Raymond J. Pickles^5,14, * Ralph S. Baric ORCID: orcid.org/0000-0001-6827-8701^4,5,15 & * J. Victor Garcia ORCID: orcid.org/0000-0003-3726-0482^1,2,3 Nature (2021)Cite this article * 186 Altmetric * Metrics details Subjects * SARS-CoV-2 * Viral pathogenesis Abstract All known recently emerged human coronaviruses probably originated in bats^1. Here we used a single experimental platform based on human lung-only mice (LoM) to demonstrate efficient in vivo replication of all recently emerged human coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) and two highly relevant endogenous pre-pandemic SARS-like bat coronaviruses. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats harbour endogenous coronaviruses capable of direct transmission into humans. Further detailed analysis of pandemic SARS-CoV-2 in vivo infection of LoM human lung tissue showed predominant infection of human lung epithelial cells, including type II pneumocytes present in alveoli and ciliated airway cells. Acute SARS-CoV-2 infection was highly cytopathic and induced a robust and sustained type I interferon and inflammatory cytokine/chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for coronavirus infection. Our results show that therapeutic and prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II-III clinical trials, dramatically inhibited SARS-CoV-2 replication in vivo and thus has significant potential for the prevention and treatment of COVID-19. Download PDF Author information Author notes 1. These authors contributed equally: Angela Wahl, Lisa E. Gralinski Affiliations 1. International Center for the Advancement of Translational Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Angela Wahl, Claire E. Johnson, Wenbo Yao, Martina Kovarova, Chandrav De & J. Victor Garcia 2. Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Angela Wahl, Claire E. Johnson, Wenbo Yao, Martina Kovarova, Chandrav De, Edward P. Browne & J. Victor Garcia 3. Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Angela Wahl, Claire E. Johnson, Wenbo Yao, Martina Kovarova, Chandrav De, Edward P. Browne & J. Victor Garcia 4. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Lisa E. Gralinski, Kenneth H. Dinnon III, Kendra Gully, Alexandra Schafer, Sarah R. Leist & Ralph S. Baric 5. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Kenneth H. Dinnon III, Edward P. Browne, Raymond J. Pickles & Ralph S. Baric 6. Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Hongwei Liu, Halina M. Krzystek, Tanzila Zaman, Paul O. Grant & Corbin D. Jones 7. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Hongwei Liu, Halina M. Krzystek, Tanzila Zaman, Paul O. Grant & Corbin D. Jones 8. Microscopy Services Laboratory, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Victoria J. Madden & Kristen K. White 9. Emory Institute of Drug Development (EIDD), Emory University, Atlanta, GA, USA Gregory R. Bluemling, Alexander A. Kolykhalov & George Painter 10. Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA, USA Gregory R. Bluemling, Alexander A. Kolykhalov, Michael G. Natchus & George Painter 11. Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Frederic B. Askin 12. Department of Pharmacology and Chemical Biology, Emory University, Atlanta, GA, USA George Painter 13. UNC HIV Cure Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Edward P. Browne 14. Marsico Lung Institute, University of North Carolina, Chapel Hill, NC, USA Raymond J. Pickles 15. Rapidly Emerging Antiviral Drug Discovery Initiative, University of North Carolina, Chapel Hill, NC, USA Ralph S. Baric Authors 1. Angela Wahl View author publications You can also search for this author in PubMed Google Scholar 2. Lisa E. Gralinski View author publications You can also search for this author in PubMed Google Scholar 3. Claire E. Johnson View author publications You can also search for this author in PubMed Google Scholar 4. Wenbo Yao View author publications You can also search for this author in PubMed Google Scholar 5. Martina Kovarova View author publications You can also search for this author in PubMed Google Scholar 6. Kenneth H. Dinnon III View author publications You can also search for this author in PubMed Google Scholar 7. Hongwei Liu View author publications You can also search for this author in PubMed Google Scholar 8. Victoria J. Madden View author publications You can also search for this author in PubMed Google Scholar 9. Halina M. Krzystek View author publications You can also search for this author in PubMed Google Scholar 10. Chandrav De View author publications You can also search for this author in PubMed Google Scholar 11. Kristen K. White View author publications You can also search for this author in PubMed Google Scholar 12. Kendra Gully View author publications You can also search for this author in PubMed Google Scholar 13. Alexandra Schafer View author publications You can also search for this author in PubMed Google Scholar 14. Tanzila Zaman View author publications You can also search for this author in PubMed Google Scholar 15. Sarah R. Leist View author publications You can also search for this author in PubMed Google Scholar 16. Paul O. Grant View author publications You can also search for this author in PubMed Google Scholar 17. Gregory R. Bluemling View author publications You can also search for this author in PubMed Google Scholar 18. Alexander A. Kolykhalov View author publications You can also search for this author in PubMed Google Scholar 19. Michael G. Natchus View author publications You can also search for this author in PubMed Google Scholar 20. Frederic B. Askin View author publications You can also search for this author in PubMed Google Scholar 21. George Painter View author publications You can also search for this author in PubMed Google Scholar 22. Edward P. Browne View author publications You can also search for this author in PubMed Google Scholar 23. Corbin D. Jones View author publications You can also search for this author in PubMed Google Scholar 24. Raymond J. Pickles View author publications You can also search for this author in PubMed Google Scholar 25. Ralph S. Baric View author publications You can also search for this author in PubMed Google Scholar 26. J. Victor Garcia View author publications You can also search for this author in PubMed Google Scholar Corresponding author Correspondence to J. Victor Garcia. Supplementary information Supplementary Table 1 Human gene expression levels in the human lungs of naive and SARS-CoV-2 infected LoMs. Reporting Summary Supplementary Table 2 Differential human gene expression in the human lungs of SARS-CoV-2 infected LoMs. Rights and permissions Reprints and Permissions About this article Verify currency and authenticity via CrossMark Cite this article Wahl, A., Gralinski, L.E., Johnson, C.E. et al. SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801. Nature (2021). https://doi.org/10.1038/s41586-021-03312-w Download citation * Received: 18 September 2020 * Accepted: 29 January 2021 * Published: 09 February 2021 * DOI: https://doi.org/10.1038/s41586-021-03312-w Comments By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Download PDF Advertisement Explore content * Research articles * News * Opinion * Research Analysis * Careers * Books & Culture * Podcasts * Videos * Current Issue * Browse Issues * Collections * Subjects * Follow us on Facebook * Follow us on Twitter * Sign up for alerts * RSS feed Journal information * About the Journal * Awards Publish with us * For Authors * For Referees * Submit manuscript Search Search articles by keyword or author [ ] Search Advanced search Quick links * Explore articles by subject * Find a job * Guide to authors * Editorial policies Nature ISSN 1476-4687 (online) nature.com sitemap Nature portfolio * About us * Press releases * Press office * Contact us * * * Discover content * Journals A-Z * Articles by subject * Nano * Protocol Exchange * Nature Index Publishing policies * Nature portfolio policies * Open access Author & Researcher services * Reprints & permissions * Research data * Language editing * Scientific editing * Nature Masterclasses * Nature Research Academies Libraries & institutions * Librarian service & tools * Librarian portal * Open research * Recommend to library Advertising & partnerships * Advertising * Partnerships & Services * Media kits * Branded content Career development * Nature Careers * Nature Conferences * Nature events Regional websites * Nature China * Nature India * Nature Japan * Nature Korea * Nature Middle East Legal & Privacy * Privacy Policy * Use of cookies * Manage cookies/Do not sell my data * Legal notice * Accessibility statement * Terms & Conditions * California Privacy Statement Springer Nature (c) 2021 Springer Nature Limited Close Nature Briefing Sign up for the Nature Briefing newsletter -- what matters in science, free to your inbox daily. Email address [ ] Sign up [ ] I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Close Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing * *