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Broad Spectrum Antiviral Properties of Cardiotonic Steroids Used as Potential Therapeutics for Emerging Coronavirus Infections.
Jin, Young-Hee; Jeon, Sangeun; Lee, Jihye; Kim, Seungtaek; Jang, Min Seong; Park, Chul Min; Song, Jong Hwan; Kim, Hyoung Rae; Kwon, Sunoh.
  • Jin YH; KM Application Center, Korea Institute of Oriental Medicine, Daegu 41062, Korea.
  • Jeon S; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea.
  • Lee J; Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Korea.
  • Kim S; Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Korea.
  • Jang MS; Zoonotic Virus Laboratory, Institut Pasteur Korea, Seongnam 13488, Korea.
  • Park CM; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea.
  • Song JH; Department of Non-Clinical Studies, Korea Institute of Toxicology, Daejeon 34114, Korea.
  • Kim HR; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea.
  • Kwon S; Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea.
Pharmaceutics ; 13(11)2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1502487
ABSTRACT
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 (IC50, 0.017~0.027 µM); bufalin showed the most potent anti-SARS-CoV and SARS-CoV-2 activity (IC50, 0.016~0.019 µM); cinobufotalin and resibufogenin showed comparatively low anti-coronavirus activity (IC50, 0.231~1.612 µM). 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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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article