n/a
Article Publish Status: FREE
Abstract Title:

Rosmarinic Acid Exhibits Broad Anti-Enterovirus A71 Activity by Inhibiting the Interaction between the Five-Fold Axis of Capsid VP1 and Cognate Sulfated Receptors.

Abstract Source:

Emerg Microbes Infect. 2020 May 13:1-37. Epub 2020 May 13. PMID: 32397909

Abstract Author(s):

Chung-Fan Hsieh, Jia-Rong Jheng, Guan-Hua Lin, Yu-Li Chen, Jin-Yuan Ho, Chien-Jou Liu, Kuei-Yang Hsu, Yuan-Siao Chen, Yoke Fun Chan, Hui-Ming Yu, Pei-Wen Hsieh, Jyh-Haur Chern, Jim-Tong Horng

Article Affiliation:

Chung-Fan Hsieh

Abstract:

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 N104 K 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 tobe 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.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Antiviral Agents : CK(1307) : AC(596)

Print Options


Key Research Topics

Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2021 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.