Baicalein suppresses Coxsackievirus B3 replication by inhibiting caspase-1 and viral protease 2A

Virol Sin. 2024 Aug;39(4):685-693. doi: 10.1016/j.virs.2024.07.003. Epub 2024 Jul 16.

Abstract

Myocarditis is an inflammatory disease of the cardiac muscle and one of the primary causes of dilated cardiomyopathy. Group B coxsackievirus (CVB) is one of the leading causative pathogens of viral myocarditis, which primarily affects children and young adults. Due to the lack of vaccines, the development of antiviral medicines is crucial to controlling CVB infection and the progression of myocarditis. In this study, we investigated the antiviral effect of baicalein, a flavonoid extracted from Scutellaria baicaleinsis. Our results demonstrated that baicalein treatment significantly reduced cytopathic effect and increased cell viability in CVB3-infected cells. In addition, significant reductions in viral protein 3D, viral RNA, and viral particles were observed in CVB3-infected cells treated with baicalein. We found that baicalein exerted its inhibitory effect in the early stages of CVB3 infection. Baicalein also suppressed viral replication in the myocardium and effectively alleviated myocarditis induced by CVB3 infection. Our study revealed that baicalein exerts its antiviral effect by inhibiting the activity of caspase-1 and viral protease 2A. Taken together, our findings demonstrate that baicalein has antiviral activity against CVB3 infection and may serve as a potential therapeutic option for the myocarditis caused by enterovirus infection.

Keywords: 2A protease; Baicalein; Caspase-1; Coxsackievirus B (CVB); Myocarditis.

MeSH terms

  • Animals
  • Antiviral Agents* / pharmacology
  • Caspase 1* / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Coxsackievirus Infections / drug therapy
  • Coxsackievirus Infections / virology
  • Cysteine Endopeptidases / metabolism
  • Cytopathogenic Effect, Viral / drug effects
  • Enterovirus B, Human* / drug effects
  • Enterovirus B, Human* / physiology
  • Flavanones* / pharmacology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis* / drug therapy
  • Myocarditis* / virology
  • Scutellaria baicalensis / chemistry
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication* / drug effects

Substances

  • baicalein
  • Flavanones
  • Antiviral Agents
  • Caspase 1
  • Viral Proteins
  • picornain 2A, Picornavirus
  • Cysteine Endopeptidases