An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice
Catastrophic consequences
Abstract
INTRODUCTION
RESULTS
NHC potently inhibits MERS-CoV and newly emerging SARS-CoV-2 replication
NHC is highly active against SARS-CoV-2, MERS-CoV, and SARS-CoV in primary human airway epithelial cell cultures
NHC is effective against remdesivir-resistant virus and multiple distinct zoonotic CoV
NHC antiviral activity is associated with increased viral mutation rates
Therapeutic EIDD-2801 reduces SARS-CoV replication and pathogenesis
EIDD-2801 prophylactic and therapeutic efficacy correlates with increased MERS-CoV mutation rate
DISCUSSION
MATERIALS AND METHODS
Study design
Ethics regulation of laboratory animals
Compounds
Cell cultures
Virus strains
In vitro antiviral activity experiments
MERS-nLUC in Calu-3
SARS-CoV-2 in Calu-3
SARS-CoV-2 in Vero E6
SARS-CoV, MERS-CoV, and SARS-CoV-2 in HAE
qRT-PCR approach to assess cytotoxicity
MERS-CoV genomic RNA qRT-PCR
Quantification of SARS-CoV-2 viral RNA genome copy number by qRT-PCR
Primer ID and deep sequencing
In vivo experiments
Whole-body plethysmography
ALI histological assessment tools
American Thoracic Society lung injury scoring tool
DAD tool
nsp12 phylogenetic analysis and conservation modeling
Statistical analysis
Funding
Supplementary Material
Summary
Resources
REFERENCES AND NOTES
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April 2020
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- Timothy P. Sheahan et al.
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