Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model

The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally admin...

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Published inNature communications Vol. 12; no. 1; p. 2295
Main Authors Rosenke, Kyle, Hansen, Frederick, Schwarz, Benjamin, Feldmann, Friederike, Haddock, Elaine, Rosenke, Rebecca, Barbian, Kent, Meade-White, Kimberly, Okumura, Atsushi, Leventhal, Shanna, Hawman, David W., Ricotta, Emily, Bosio, Catharine M., Martens, Craig, Saturday, Greg, Feldmann, Heinz, Jarvis, Michael A.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 16.04.2021
Nature Publishing Group
Nature Portfolio
Subjects
13/106
38/1
38/77
631/326/22/1295
631/326/596/4130
82/51
Administration, Oral
Animals
Antiviral agents
Antiviral Agents - administration & dosage
Chlorocebus aethiops
Coronaviruses
COVID-19
COVID-19 - drug therapy
COVID-19 - virology
Cytidine - administration & dosage
Cytidine - analogs & derivatives
Disease Models, Animal
Exposure
Humanities and Social Sciences
Humans
Hydroxylamines - administration & dosage
Infections
Mesocricetus
Model testing
multidisciplinary
Nucleoside analogs
Nucleosides
Oral administration
Pandemics
Replication
Risk
Risk exposure
SARS-CoV-2 - drug effects
SARS-CoV-2 - isolation & purification
SARS-CoV-2 - physiology
Science
Science (multidisciplinary)
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Vaccines
Vero Cells
Viral diseases
Virus Replication - drug effects
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Abstract The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients. While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.
AbstractList The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients. While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.
While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.
The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.
The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2. Here, Rosenke et al. provide evidence that orally delivered MK-4482, a nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model.
ArticleNumber 2295
Author Jarvis, Michael A.
Barbian, Kent
Feldmann, Heinz
Feldmann, Friederike
Leventhal, Shanna
Bosio, Catharine M.
Okumura, Atsushi
Hansen, Frederick
Haddock, Elaine
Schwarz, Benjamin
Ricotta, Emily
Rosenke, Rebecca
Hawman, David W.
Martens, Craig
Saturday, Greg
Meade-White, Kimberly
Rosenke, Kyle
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Snippet The COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use...
While vaccines protecting against SARS-CoV-2 infection are approved, currently, there are no drugs suitable for high-risk exposure use against SARS-CoV-2....
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Chlorocebus aethiops
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COVID-19
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Cytidine - analogs & derivatives
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Exposure
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Infections
Mesocricetus
Model testing
multidisciplinary
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Nucleosides
Oral administration
Pandemics
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Risk
Risk exposure
SARS-CoV-2 - drug effects
SARS-CoV-2 - isolation & purification
SARS-CoV-2 - physiology
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Science (multidisciplinary)
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Vaccines
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Virus Replication - drug effects
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Title Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model
URI https://link.springer.com/article/10.1038/s41467-021-22580-8
https://www.ncbi.nlm.nih.gov/pubmed/33863887
https://www.proquest.com/docview/2513413903
https://search.proquest.com/docview/2514610210
https://pubmed.ncbi.nlm.nih.gov/PMC8052374
https://doaj.org/article/9a78a63a312847aa863ae1016f4d581a
Volume 12
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