51. Evaluation of the virucidal effects of rosmarinic acid against enterovirus 71 infection via in vitro and in vivo study
- Author
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Yu-Jen Yu, Wen-Yu Lin, and Tzyy-Rong Jinn
- Subjects
0301 basic medicine ,Virus Replication ,Neonatal mice ,Antiviral Agents ,Depsides ,lcsh:Infectious and parasitic diseases ,Pathogenesis ,Inhibitory Concentration 50 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Therapeutic index ,Multiplicity of infection ,Cytopathogenic Effect, Viral ,In vivo ,Cell Line, Tumor ,Virology ,Enterovirus Infections ,Enterovirus 71 ,Animals ,Humans ,lcsh:RC109-216 ,Infectivity ,biology ,Research ,Infectious dose ,biology.organism_classification ,Enterovirus A, Human ,Molecular Docking Simulation ,Rosmarinic acid ,030104 developmental biology ,Infectious Diseases ,Animals, Newborn ,Cinnamates ,Cell culture ,Molecular docking ,030211 gastroenterology & hepatology ,Virucidal efficacy ,Herbal medicine - Abstract
Background 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. Methods 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. Results RA showed a strong protective effect against EV71 infection in human rhabdomyosarcoma cells when the multiplicity of infection was 1, with a low IC50 value (4.33 ± 0.18 μM) and high therapeutic index (340). RA not only protected cells from EV71-induced cytopathic effects, but also from EV71-induced apoptosis. The results of time-of-addition analysis demonstrated that the inhibitory activity of RA was highest at the early stage of viral infection. Consistent with this, the infectivity of EV71 in the early stage of viral infection also was observed to be limited in neonatal mice treated with RA. Further, molecular docking predicts that RA could replace the natural pocket factor within the VP1 capsid-binding hydrophobic pocket. Conclusions 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.
- Published
- 2019
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