Your browser doesn't support javascript.
loading
Rosmarinic acid exhibits broad anti-enterovirus A71 activity by inhibiting the interaction between the five-fold axis of capsid VP1 and cognate sulfated receptors.
Hsieh, Chung-Fan; Jheng, Jia-Rong; Lin, Guan-Hua; Chen, Yu-Li; Ho, Jin-Yuan; Liu, Chien-Jou; Hsu, Kuei-Yang; Chen, Yuan-Siao; Chan, Yoke Fun; Yu, Hui-Ming; Hsieh, Pei-Wen; Chern, Jyh-Haur; Horng, Jim-Tong.
Afiliación
  • Hsieh CF; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Jheng JR; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Lin GH; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Chen YL; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Ho JY; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Liu CJ; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Hsu KY; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Chen YS; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Chan YF; Department of Medical Microbiology, University Malaya, Kuala Lumpur, Malaysia.
  • Yu HM; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • Hsieh PW; Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
  • Chern JH; Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
  • Horng JT; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Emerg Microbes Infect ; 9(1): 1194-1205, 2020 Dec.
Article en En | MEDLINE | ID: mdl-32397909
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, Salvia miltiorrhiza (Danshen), were screened for anti-EV-A71. We identified a natural product, rosmarinic acid (RA), as a potential inhibitor of EV-A71 by cell-based antiviral assay and in vivo mouse model. Results also show that RA may affect the early stage of viral infection and may target viral particles directly, thereby interfering with virus-P-selectin glycoprotein ligand-1 (PSGL1) and virus-heparan sulfate interactions without abolishing the interaction between the virus and scavenger receptor B2 (SCARB2). Sequencing of the plaque-purified RA-resistant viruses revealed a N104K mutation in the five-fold axis of the structural protein VP1, which contains positively charged amino acids reportedly associated with virus-PSGL1 and virus-heparan sulfate interactions via electrostatic attraction. The plasmid-derived recombinant virus harbouring this mutation was confirmed to be refractory to RA inhibition. Receptor pull-down showed that this non-positively charged VP1-N104 is critical for virus binding to heparan sulfate. As the VP1-N104 residue is conserved among different EV-A71 strains, RA may be useful for inhibiting EV-A71 infection, even for emergent virus variants. Our study provides insight into the molecular mechanism of virus-host interactions and identifies a promising new class of inhibitors based on its antiviral activity and broad spectrum effects against a range of EV-A71.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Cinamatos / Enterovirus Humano A / Salvia miltiorrhiza / Proteínas de la Cápside / Infecciones por Enterovirus / Depsidos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Emerg Microbes Infect Año: 2020 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Cinamatos / Enterovirus Humano A / Salvia miltiorrhiza / Proteínas de la Cápside / Infecciones por Enterovirus / Depsidos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Emerg Microbes Infect Año: 2020 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos