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The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15

Shutoku Matsuyama, Miyuki Kawase, Naganori Nao, Kazuya Shirato, Makoto Ujike, Wataru Kamitani, Masayuki Shimojima, Shuetsu Fukushi
doi: https://doi.org/10.1101/2020.03.11.987016
Shutoku Matsuyama
1Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan
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  • For correspondence: matuyama@nih.go.jp
Miyuki Kawase
1Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan
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Naganori Nao
1Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan
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Kazuya Shirato
1Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan
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Makoto Ujike
2Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan
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Wataru Kamitani
3Department of Infectious Diseases and Host Defense, Gunma University Graduate School of Medicine
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Masayuki Shimojima
4Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan
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Shuetsu Fukushi
4Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan
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Abstract

Steroid compounds, which are expected to have dual functions in blocking host inflammation and MERS-CoV replication, were screened from a chemical library. Within this library, ciclesonide, an inhaled corticosteroid, suppressed human coronavirus replication in cultured cells, but did not suppress replication of respiratory syncytial virus or influenza virus. The effective concentration of ciclesonide to block SARS-CoV-2 (the cause of COVID-19) replication (EC90) was 6.3 μM. After the eleventh consecutive MERS-CoV passage in the presence of ciclesonide, a resistant mutation was generated, which resulted in an amino acid substitution (A25V) in nonstructural protein (NSP) 15, as identified using reverse genetics. A recombinant virus with the mutation was also resistant to ciclesonide suppression of viral replication. These observations suggest that the effect of ciclesonide was specific to coronavirus, suggesting this is a candidate drug for treatment of patients suffering MERS or COVID-19.

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Posted March 12, 2020.
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The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15
Shutoku Matsuyama, Miyuki Kawase, Naganori Nao, Kazuya Shirato, Makoto Ujike, Wataru Kamitani, Masayuki Shimojima, Shuetsu Fukushi
bioRxiv 2020.03.11.987016; doi: https://doi.org/10.1101/2020.03.11.987016
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The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral NSP15
Shutoku Matsuyama, Miyuki Kawase, Naganori Nao, Kazuya Shirato, Makoto Ujike, Wataru Kamitani, Masayuki Shimojima, Shuetsu Fukushi
bioRxiv 2020.03.11.987016; doi: https://doi.org/10.1101/2020.03.11.987016

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