ATR inhibitor blocks SARS-CoV-2
DDR/ATR inhibitor berzosertib potently blocks SARS-CoV-2 replication in cell culture.
Source
Antiviral drug screen identifies DNA-damage response inhibitor as potent blocker of SARS-CoV-2 replication
Study at a glance
- Design
- Animal / in-vitro — Medium-throughput SARS-CoV-2 antiviral screen of kinase inhibitors in Vero E6 cells
- N
- ~430 kinase inhibitors screened; cell-assay study without a human sample N
- Population
- Vero E6 cells infected with SARS-CoV-2
- Outcome
- Antiviral activity of kinase inhibitors (notably berzosertib/ATR)
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ATR inhibitor blocks SARS-CoV-2
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430 kinase inhibitors screened.
To evaluate the antiviral properties of cellular protein kinase inhibitors, we performed medium-throughput primary drug screening (A) by selecting a drug compound library that broadly covers 430 kinase inhibitors with the screening compound concentration that would have potent anti-viral activity with low levels of toxicity.
Screen size?
broadly covers 430 kinase inhibitors
What they did
Built a Vero E6 SARS-CoV-2 assay and screened ~430 kinase inhibitors for antiviral activity with low toxicity.
What they found
Berzosertib (ATR inhibitor) showed strong antiviral activity; 100 nM fully blocked replication at 48 hpi in their assay.
The limits
What it doesn't show
Not a completed human clinical efficacy trial for COVID-19.
Key terms
- SARS-CoV-2
- COVID-19 coronavirus.
- ATR
- DNA-damage response kinase.
- Berzosertib
- ATR inhibitor (M6620).
- TCID50
- Infectious titer assay endpoint.
- Vero E6
- Primate cell line for viral culture.
- DDR
- DNA damage response pathway.
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Library size:
Common questions
Library size?
430 kinase inhibitors.
Hit drug?
Berzosertib.
100 nM effect?
Complete inhibition at 48 hpi.
Target?
ATR kinase / DDR.
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