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| Status |
Public on Sep 23, 2020 |
| Title |
SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801 |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
All coronaviruses known to have recently emerged as human pathogens probably originated in bats1. Here we use a single experimental platform based on immunodeficient mice implanted with human lung tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. 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 contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801?an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials?markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
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| Overall design |
Human lung-only mice (LoM) were used as an in vivo model to evaluate infection of lung tissue with recombinant coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2 as well as full length bat coronaviruses WIV1 and SHC014 (12, 13, 35, 36). Viruses were directly injected into the human lung tissue of LoMs and lung tissue collected either 2, 6, or 14 days post-exposure for virus titer determination and/or analysis by histology, electron microscopy, or RNA-seq.
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| Contributor(s) |
Wahl AR, Baric RS, Pickles RJ, Browne EP, Jones CD |
| Citation(s) |
33561864 |
| |
| Submission date |
Jul 28, 2020 |
| Last update date |
Jul 30, 2021 |
| Contact name |
Paul O Grant |
| E-mail(s) |
paul_grant@med.unc.edu
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| Phone |
7043145422
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| Organization name |
UNC SOM
|
| Department |
BARC
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| Street address |
3105 Neuoscience Research Building
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27516 |
| Country |
USA |
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| Platforms (1) |
| GPL25526 |
Illumina NovaSeq 6000 (Homo sapiens; Mus musculus) |
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| Samples (13)
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| Relations |
| BioProject |
PRJNA649246 |
| SRA |
SRP273970 |
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