rosmarinic-acid and Enterovirus-Infections

Enterovirus A71 (EV-A71), a positive-stranded RNA virus of the Picornaviridae family, may cause neurological complications or fatality in children. We examined specific factors responsible for this virulence using a chemical genetics approach. Known compounds from an anti-EV-A71 herbal medicine,

Topics: Animals; Antiviral Agents; Capsid Proteins; Cell Line; Cinnamates; Depsides; Disease Models, Animal; Drug Evaluation, Preclinical; Enterovirus A, Human; Enterovirus Infections; Heparitin Sulfate; Humans; Jurkat Cells; Membrane Glycoproteins; Mice; Mutation; Plant Extracts; Protein Binding; Rosmarinic Acid; Salvia miltiorrhiza; Static Electricity; Virulence Factors

Although enterovirus 71 (EV71) is an important public health threat, especially in the Asia-Pacific region, there are still no effective drugs or vaccines to treat and prevent EV71 infection. Therefore, it is critical to develop prophylactic and therapeutic agents against EV71. Rosmarinic acid (RA), a phytochemical, has been discovered to possess a broad spectrum of biological activities.. The virucidal effects of RA on EV71 were determined by MTT, western blot, median cell culture infectious dose, apoptosis detection, plaque reduction, semi-quantitative real-time polymerase chain reaction, immunofluorescence detection, molecular docking analysis, and mouse protection assay.. RA showed a strong protective effect against EV71 infection in human rhabdomyosarcoma cells when the multiplicity of infection was 1, with a low IC. This study suggests that RA has the potential to be developed as an antiviral agent against initial EV71 infection to prevent or reduce EV71-induced pathogenesis and complications, since RA can effectively reduce EV71 infection in the early stages of viral infection.

Topics: Animals; Animals, Newborn; Antiviral Agents; Cell Line, Tumor; Cinnamates; Cytopathogenic Effect, Viral; Depsides; Enterovirus A, Human; Enterovirus Infections; Humans; Inhibitory Concentration 50; Mice; Molecular Docking Simulation; Rosmarinic Acid; Virus Replication

The aim of this study was to identify the active ingredients responsible for the anti-EV71 activity produced by Salvia miltiorrhiza extracts. A pGS-EV71 IRES-based bicistronic reporter assay platform was used for rapid analysis of compounds that could specifically inhibit EV71 viral IRES-mediated translation. The analysis identified 2 caffeic acid derivatives, magnesium lithospermate B (MLB) and rosmarinic acid (RA), which suppressed EV71 IRES-mediated translation at concentrations of 30μg/ml. We also found that MLB and RA inhibited EV71 infection when they were added to RD cells during the viral absorption stage. MLB had a low IC50 value of 0.09mM and a high TI value of 10.52. In contrast, RA had an IC50 value of 0.50mM with a TI value of 2.97. MLB and RA (100µg/ml) also reduced EV71 viral particle production and significantly decreased VP1 protein production. We propose that these two derivatives inhibit EV71 viral entry into cells and viral IRES activity, thereby reducing viral particle production and viral RNA expression and blocking viral VP1 protein translation. This study provides useful information for the development of anti-EV71 assays and reagents by demonstrating a convenient EV71 IRES-based bicistronic assay platform to screen for anti-EV71 IRES activity, and also reports 2 compounds, MLB and RA, which are responsible for the anti-EV71 activity of S. miltiorrhiza.

Topics: Animals; Antiviral Agents; Capsid Proteins; Cell Line, Tumor; Chlorocebus aethiops; Cinnamates; COS Cells; Depsides; Drugs, Chinese Herbal; Enterovirus A, Human; Enterovirus Infections; Humans; Plant Roots; Rosmarinic Acid; Salvia miltiorrhiza; Virus Replication