Synthesis and pharmacodynamic evaluation of Dihydropteridone derivatives against PDCoV in vivo and in vitro

Bioorg Chem. 2024 May:146:107322. doi: 10.1016/j.bioorg.2024.107322. Epub 2024 Mar 29.

Abstract

Porcine Delta Coronavirus (PDCoV) infection can induce serious dehydration, diarrhea and even death of piglets, which has caused huge losses to the breeding industry. PDCoV has been reported to have the potential for cross species transmission, and even reports of infecting humans have emerged. At present, there are still no effective prevention and control measures for PDCoV. In this study, we have designed and synthesized a series of unreported Dihydropteridone derivatives. All of these compounds were evaluated for the against PDCoV in vivo and in vitro for the first time. In this study, antiviral activity (17.34 ± 7.20 μM) and low cytotoxicity (>800 μM) was found in compound W8. Compound W8 exerts antiviral effect on PDCoV by inhibiting cell apoptosis and inflammatory factors caused by virus infection in vitro. In addition, lung and small intestinal lesions caused by PDCoV infection in mice could be significantly reduced by compound W8. These findings highlight the potential of compound W8 as a valuable therapeutic option against PDCoV infection, and lay a foundation for further research and development in this field.

Keywords: Antiviral activity; Apoptosis; Dihydropteridone derivatives; PDCoV; RIG-Ⅰ.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Coronavirus Infections*
  • Coronavirus*
  • Humans
  • Intestine, Small
  • Mice
  • Sulfonamides*
  • Swine

Substances

  • N-(8-aminohexyl)-5-iodonaphthalene-1-sulfonamide
  • Antiviral Agents
  • Sulfonamides