Prolonged presence of SARS-CoV-2 in a COVID-19 case with rheumatoid arthritis taking iguratimod treated with ciclesonide

Baba, Hiroaki; Kanamori, Hajime; Oshima, Kengo; Niitsuma-Sugaya, Ikumi; Takei, Kentaro; Sato, Yukio; Tokuda, Koichi; Aoyagi, Tetsuji

doi:10.1016/j.jiac.2020.06.022

Cited by 8 publications

(4 citation statements)

References 20 publications

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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

205

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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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

205

158

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show abstract

“…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: 94%

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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“…23 Recently, various studies found that people developed arthritis after having COVID-19 (Table 1). COVID-19 has been reported to be associated with RA, 24,25 psoriatic arthritis, 26 reactive arthritis, 9,27,28 seronegative erosive arthritis, 29 chronic arthritis, 30 etc. Despite ongoing research, our comprehension of COVID-19-associated arthritis is currently limited.…”

Section: Introductionmentioning

confidence: 99%

Development of nanozymes for promising alleviation of COVID-19-associated arthritis

Zhao

Zhuang

et al. 2023

Biomater. Sci.

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Prolonged presence of SARS-CoV-2 in a COVID-19 case with rheumatoid arthritis taking iguratimod treated with ciclesonide

Cited by 8 publications

References 20 publications

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 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

Development of nanozymes for promising alleviation of COVID-19-associated arthritis

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