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10.3390/pharmaceutics13111839

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suck abstract from ncbi


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pmid34834252      Pharmaceutics 2021 ; 13 (11): ä
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  • Broad Spectrum Antiviral Properties of Cardiotonic Steroids Used as Potential Therapeutics for Emerging Coronavirus Infections #MMPMID34834252
  • Jin YH; Jeon S; Lee J; Kim S; Jang MS; Park CM; Song JH; Kim HR; Kwon S
  • Pharmaceutics 2021[Nov]; 13 (11): ä PMID34834252show ga
  • Cardiotonic steroids are steroid-like natural compounds known to inhibit Na(+)/K(+)-ATPase pumps. To develop a broad-spectrum antiviral drug against the emerging coronavirus infection, this study assessed the antiviral properties of these compounds. The activity of seven types of cardiotonic steroids against the MERS-CoV, SARS-CoV, and SARS-CoV-2 coronavirus varieties was analyzed using immunofluorescence antiviral assay in virus-infected cells. Bufalin, cinobufagin, and telocinobufagin showed high anti-MERS-CoV activities (IC(50), 0.017~0.027 muM); bufalin showed the most potent anti-SARS-CoV and SARS-CoV-2 activity (IC(50), 0.016~0.019 muM); cinobufotalin and resibufogenin showed comparatively low anti-coronavirus activity (IC(50), 0.231~1.612 muM). Differentially expressed genes in Calu3 cells treated with cinobufagin, telocinobufagin, or bufalin, which had high antiviral activity during MERS-CoV infection were analyzed using QuantSeq 3' mRNA-Seq analysis and data showed similar gene expression patterns. Furthermore, the intraperitoneal administration of 10 mg/kg/day bufalin, cinobufagin, or digitoxin induced 100% death after 1, 2, and 4 days in 5-day repeated dose toxicity studies and it indicated that bufalin had the strongest toxicity. Pharmacokinetic studies suggested that telocinobufagin, which had high anti-coronavirus activity and low toxicity, had better microsomal stability, lower CYP inhibition, and better oral bioavailability than cinobufagin. Therefore, telocinobufagin might be the most promising cardiotonic steroid as a therapeutic for emerging coronavirus infections, including COVID-19.
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