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Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801
All known recently emerged human coronaviruses likely originated in bats. 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, SARS-CoV-2) and two highly relevant...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523135/ https://www.ncbi.nlm.nih.gov/pubmed/32995766 http://dx.doi.org/10.21203/rs.3.rs-80404/v1 |
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author | Wahl, Angela Gralinski, Lisa Johnson, Claire Yao, Wenbo Kovarova, Martina Dinnon, Kenneth Liu, Hongwei Madden, Victoria Krzystek, Halina De, Chandrav White, Kristen Schäfer, Alexandra Zaman, Tanzila Leist, Sarah Grant, Paul Gully, Kendra Askin, Frederic Browne, Edward Jones, Corbin Pickles, Raymond Baric, Ralph Garcia, J Victor |
author_facet | Wahl, Angela Gralinski, Lisa Johnson, Claire Yao, Wenbo Kovarova, Martina Dinnon, Kenneth Liu, Hongwei Madden, Victoria Krzystek, Halina De, Chandrav White, Kristen Schäfer, Alexandra Zaman, Tanzila Leist, Sarah Grant, Paul Gully, Kendra Askin, Frederic Browne, Edward Jones, Corbin Pickles, Raymond Baric, Ralph Garcia, J Victor |
author_sort | Wahl, Angela |
collection | PubMed |
description | All known recently emerged human coronaviruses likely originated in bats. 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, 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 harbor 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 pre-exposure prophylaxis strategy for coronavirus infection. Our results show that prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II clinical trials for the treatment of COVID-19, dramatically prevented SARS-CoV-2 infection in vivo and thus has significant potential for the prevention and treatment of COVID-19. |
format | Online Article Text |
id | pubmed-7523135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-75231352020-09-30 Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 Wahl, Angela Gralinski, Lisa Johnson, Claire Yao, Wenbo Kovarova, Martina Dinnon, Kenneth Liu, Hongwei Madden, Victoria Krzystek, Halina De, Chandrav White, Kristen Schäfer, Alexandra Zaman, Tanzila Leist, Sarah Grant, Paul Gully, Kendra Askin, Frederic Browne, Edward Jones, Corbin Pickles, Raymond Baric, Ralph Garcia, J Victor Res Sq Article All known recently emerged human coronaviruses likely originated in bats. 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, 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 harbor 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 pre-exposure prophylaxis strategy for coronavirus infection. Our results show that prophylactic administration of EIDD-2801, an oral broad spectrum antiviral currently in phase II clinical trials for the treatment of COVID-19, dramatically prevented SARS-CoV-2 infection in vivo and thus has significant potential for the prevention and treatment of COVID-19. American Journal Experts 2020-09-24 /pmc/articles/PMC7523135/ /pubmed/32995766 http://dx.doi.org/10.21203/rs.3.rs-80404/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Wahl, Angela Gralinski, Lisa Johnson, Claire Yao, Wenbo Kovarova, Martina Dinnon, Kenneth Liu, Hongwei Madden, Victoria Krzystek, Halina De, Chandrav White, Kristen Schäfer, Alexandra Zaman, Tanzila Leist, Sarah Grant, Paul Gully, Kendra Askin, Frederic Browne, Edward Jones, Corbin Pickles, Raymond Baric, Ralph Garcia, J Victor Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 |
title | Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 |
title_full | Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 |
title_fullStr | Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 |
title_full_unstemmed | Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 |
title_short | Acute SARS-CoV-2 Infection is Highly Cytopathic, Elicits a Robust Innate Immune Response and is Efficiently Prevented by EIDD-2801 |
title_sort | acute sars-cov-2 infection is highly cytopathic, elicits a robust innate immune response and is efficiently prevented by eidd-2801 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523135/ https://www.ncbi.nlm.nih.gov/pubmed/32995766 http://dx.doi.org/10.21203/rs.3.rs-80404/v1 |
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