Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57

Mengjie Wang; Qi Dong; Hua Wang; Yaqing He; Ying Chen; Hong Zhang; Rong Wu; Xinchun Chen; Boping Zhou; Jason He; Hsiang-Fu Kung; Canhua Huang; Yuquan Wei; Jian-dong Huang; Hongxi Xu; Ming-Liang He

doi:10.18632/oncotarget.7122

Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57

Oncotarget. 2016 Feb 23;7(8):8797-808. doi: 10.18632/oncotarget.7122.

Authors

Mengjie Wang^{1

2}, Qi Dong^{2

3

4}, Hua Wang³, Yaqing He⁵, Ying Chen⁴, Hong Zhang¹, Rong Wu¹, Xinchun Chen⁶, Boping Zhou⁶, Jason He⁷, Hsiang-Fu Kung^{2

3}, Canhua Huang⁸, Yuquan Wei⁸, Jian-dong Huang⁹, Hongxi Xu¹, Ming-Liang He⁴

Affiliations

¹ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
³ Stanley Ho Center for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China.
⁴ Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
⁵ Shenzhen Center for Disease Control and Prevention (Shenzhen CDC), Shenzhen, China.
⁶ Institute of Infectious Diseases, The 3rd Peoples' Hospital of Shenzhen, Shenzhen, China.
⁷ College of Letter and Sciences, University of California at Berkeley, Berkeley, CA, USA.
⁸ State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
⁹ School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China.

Abstract

There is no effective drug to treat EV71 infection yet. Traditional Chinese herbs are great resources for novel antiviral compounds. Here we showed that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection.

Keywords: ERp57; Oblongifolin M; antiviral; enterovirus 71.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
Blotting, Western
Electrophoresis, Gel, Two-Dimensional
Enterovirus A, Human / pathogenicity
Enterovirus Infections / metabolism
Enterovirus Infections / pathology
Enterovirus Infections / prevention & control*
Enterovirus Infections / virology
Garcinia / chemistry*
Genome, Viral
Humans
Plant Extracts / pharmacology*
Protein Disulfide-Isomerases / antagonists & inhibitors
Protein Disulfide-Isomerases / genetics
Protein Disulfide-Isomerases / metabolism*
Proteomics
RNA, Messenger / genetics
RNA, Small Interfering / genetics
RNA, Viral / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Rhabdomyosarcoma / metabolism
Rhabdomyosarcoma / pathology
Rhabdomyosarcoma / prevention & control*
Rhabdomyosarcoma / virology
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Terpenes / pharmacology*
Tumor Cells, Cultured
Viral Proteins / metabolism
Virus Replication / drug effects*

Substances

Antiviral Agents
Plant Extracts
RNA, Messenger
RNA, Small Interfering
RNA, Viral
Terpenes
Viral Proteins
Protein Disulfide-Isomerases
PDIA3 protein, human