Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus In Vitro and In Vivo.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI
    • Subject Terms:
      Benzylisoquinolines*/pharmacology ; Coronavirus Infections*/drug therapy ; Coronavirus Infections*/pathology ; Coronavirus Infections*/veterinary ; Porcine epidemic diarrhea virus* ; Swine Diseases*/pathology; Animals ; Diarrhea ; Swine
    • Abstract:
      Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae that causes severe diarrhea and high mortality in neonatal suckling piglets. Currently, there is no effective medication against this pathogen. Cepharanthine (CEP), tetrandrine (TET), and fangchinoline (FAN) are natural bis-benzylisoquinoline alkaloids with anti-inflammatory, antitumor, and antiviral properties. Here, we first found that CEP, TET, and FAN had anti-PEDV activity with IC 50 values of 2.53, 3.50, and 6.69 μM, respectively. The compounds could block all the processes of viral cycles, but early application of the compounds before or during virus infection was advantageous over application at a late stage of virus replication. FAN performed inhibitory function more efficiently through interfering with the virus entry and attachment processes or through attenuating the virus directly. CEP had a more notable effect on virus entry. With the highest SI index of 11.8 among the three compounds, CEP was chosen to carry out animal experiments. CEP in a safe dosage of 11.1 mg/kg of body weight could reduce viral load and pathological change of piglet intestinal tracts caused by PEDV field strain challenge, indicating that CEP efficiently inhibited PEDV infection in vivo. All of these results demonstrated that the compounds of bis-benzylisoquinoline alkaloids could inhibit PEDV proliferation efficiently and had the potential of being developed for PED prevention and treatment.
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    • Contributed Indexing:
      Keywords: PEDV; antiviral effect; bis-benzylisoquinoline alkaloids; cepharanthine; fangchinoline; in vitro; in vivo; tetrandrine
    • Accession Number:
      0 (Benzylisoquinolines)
    • Publication Date:
      Date Created: 20220624 Date Completed: 20220627 Latest Revision: 20220721
    • Publication Date:
      20240105
    • Accession Number:
      PMC9228057
    • Accession Number:
      10.3390/v14061231
    • Accession Number:
      35746702