A Case of Coronavirus Disease 2019 Treated With Ciclesonide

Nakajima, Kento; Ogawa, Fumihiro; Sakai, Kazuya; Uchiyama, Mitsuaki; Oyama, Yutaro; Kato, Hideaki; Takeuchi, Ichiro

doi:10.1016/j.mayocp.2020.04.007

Cited by 22 publications

(24 citation statements)

References 4 publications

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“…The potential multitarget activity of ciclesonide may help to overcome drug resistance in COVID-19. Additional favorable results were reported from studies identifying that ciclesonide inhalant may improve the respiratory status in severe COVID-19-induced pneumonia [ 20 ] and in cases of mild- to mid-stage COVID-19 [ 21 ]. Ciclesonide is a safe drug commonly used for inhalation in premature babies and newborns, as well as the elderly.…”

Section: Discussionmentioning

confidence: 93%

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

et al. 2020

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The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method applied for small molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing.

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Section: Discussionmentioning

confidence: 93%

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

et al. 2020

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“…The treatment regime involves inhalation of 400 μg ciclesonide (two or three times per day; total, 1200 μg/day) for 2 weeks. Three cases of COVID-19 pneumonia treated successfully with ciclesonide have been reported on November 2, 2020 by guest http://jvi.asm.org/ Downloaded from (28), as have several case reports (29)(30)(31). None of these studies reported significant side effects.…”

Section: Discussionmentioning

confidence: 99%

The Inhaled Steroid Ciclesonide Blocks SARS-CoV-2 RNA Replication by Targeting the Viral Replication-Transcription Complex in Cultured Cells

Matsuyama

Kawase

Nao

et al. 2020

J Virol

203

158

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Here, we screened steroid compounds to obtain a drug expected to block host inflammatory responses and MERS-CoV replication. Ciclesonide, an inhaled corticosteroid, suppressed replication of MERS-CoV and other coronaviruses, including SARS-CoV-2, the cause of COVID-19, in cultured cells. The effective concentration (EC90) of ciclesonide for SARS-CoV-2 in differentiated human bronchial tracheal epithelial cells was 0.55 μM. Eight consecutive passages of 43 SARS-CoV-2 isolates in the presence of ciclesonide generated 15 resistant mutants harboring single amino acid substitutions in non-structural protein 3 (nsp3) or nsp4. Of note, ciclesonide suppressed replication of all these mutants by 90% or more, suggesting that these mutants cannot completely overcome ciclesonide blockade. Under the microscope, the viral RNA replication-transcription complex in cells, which is thought to be detectable using antibodies specific for nsp3 and double stranded RNA, was observed to fall in the presence of ciclesonide in a concentration-dependent manner. These observations indicate that the suppressive effect of ciclesonide on viral replication is specific to coronaviruses, highlighting it as a candidate drug for the treatment of COVID-19 patients. IMPORTANCE The outbreak of SARS-CoV-2, the cause of COVID-19, is ongoing. New and effective antiviral agents that combat the disease are needed urgently. Here, we found that an inhaled corticosteroid, ciclesonide, suppresses replication of coronaviruses, including beta-coronaviruses (MHV-2, MERS-CoV, SARS-CoV, and SARS-CoV-2) and an alpha-coronavirus (HCoV-229E), in cultured cells. Ciclesonide is safe; indeed, it can be administered to infants at high concentrations. Thus, ciclesonide is expected to be a broad-spectrum antiviral drug that is effective against many members of the coronavirus family. It could be prescribed for treatment of MERS and COVID-19.

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“…The treatment regime involves inhalation of 400 μ g ciclesonide (two or three times per day) for 2 weeks. Three cases of COVID-19 pneumonia treated successfully with ciclesonide have been reported (15), as have several case reports (16)(17)(18). None of these studies reported significant side effects.…”

Section: Introductionmentioning

confidence: 96%

The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells

Matsuyama

Kawase

Nao

et al. 2020

Preprint

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We screened steroid compounds to obtain a drug expected to block host inflammatory responses and MERS-CoV replication. Ciclesonide, an inhaled corticosteroid, suppressed replication of MERS-CoV and other coronaviruses, including SARS-CoV-2, the cause of COVID-19, in cultured cells. The effective concentration (EC90) of ciclesonide for SARS-CoV-2 in differentiated human bronchial tracheal epithelial cells was 0.55 μM. Ciclesonide inhibited formation of double membrane vesicles, which anchor the viral replication-transcription complex in cells. Eight consecutive passages of 43 SARS-CoV-2 isolates in the presence of ciclesonide generated 15 resistant mutants harboring single amino acid substitutions in non-structural protein 3 (nsp3) or nsp4. Of note, ciclesonide still suppressed replication of all these mutants by 90% or more, suggesting that these mutants cannot completely overcome ciclesonide blockade. These observations indicate that the suppressive effect of ciclesonide on viral replication is specific to coronaviruses, highlighting it as a candidate drug for the treatment of COVID-19 patients.

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A Case of Coronavirus Disease 2019 Treated With Ciclesonide

Cited by 22 publications

References 4 publications

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method

The Inhaled Steroid Ciclesonide Blocks SARS-CoV-2 RNA Replication by Targeting the Viral Replication-Transcription Complex in Cultured Cells

The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells

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