Abstract
SARS-CoV-2 has caused an extensive pandemic of COVID-19 all around the world. Key viral enzymes are suitable molecular targets for the development of new antivirals against SARS-CoV-2 which could represent potential treatments of the corresponding disease. With respect to its essential role in the replication of viral RNA, RNA-dependent RNA polymerase (RdRp) is one of the prime targets. HeE1-2Tyr and related derivatives were originally discovered as inhibitors of the RdRp of flaviviruses. Here, we present that these pyridobenzothiazole derivatives also significantly inhibit SARS-CoV-2 RdRp, as demonstrated using both polymerase- and cell-based antiviral assays.
Keywords:
COVID-19; RNA-dependent RNA polymerase; SAR-CoV-2; antiviral agents; non-nucleotide inhibitor.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Monophosphate / analogs & derivatives
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Adenosine Monophosphate / pharmacology
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Alanine / analogs & derivatives
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Alanine / pharmacology
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Animals
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Antiviral Agents / pharmacology*
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Benzothiazoles / pharmacology*
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Cell Line
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Cell Survival / drug effects
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Coronavirus RNA-Dependent RNA Polymerase / antagonists & inhibitors*
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology*
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Humans
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Microbial Sensitivity Tests
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Pyridones / pharmacology*
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SARS-CoV-2 / drug effects*
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SARS-CoV-2 / enzymology
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SARS-CoV-2 / physiology
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Virus Replication / drug effects*
Substances
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Antiviral Agents
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Benzothiazoles
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Enzyme Inhibitors
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HeE1-2Tyr
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Pyridones
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remdesivir
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Adenosine Monophosphate
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Coronavirus RNA-Dependent RNA Polymerase
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NSP12 protein, SARS-CoV-2
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Alanine