Chlorogenic Acid Inhibits the Replication and Viability of Enterovirus 71 In Vitro

Xiang Li,Hongjun Peng,Weifeng Shi,Li Zhang,Yun Ji,Xueling Hou,Qingbo Jiang,Yuyue Wang,Mei Shi,Yuanyuan Liu,Paul G Thomas

doi:10.1371/journal.pone.0076007

Abstract

Enterovirus 71 (EV71) is an etiology for a number of diseases in humans. Traditional Chinese herbs have been reported to be effective for treating EV71 infection. However, there is no report about the antiviral effects of CHA against EV71. In this study, plaque reduction assay demonstrated that the inhibitory concentration 50% (IC50) of CHA on EV71 replication is 6.3 µg/ml. When both CHA (20 µg/ml) and EV71 were added, or added post-infection at different time points, CHA was able to effectively inhibit EV71 replication between 0 and 10 h. In addition, CHA inhibited EV71 2A transcription and translation in EV71-infected RD cells, but did not affect VP1, 3C, and 3D expression. Furthermore, CHA inhibited secretions of IL-6, TNF-α, IFN-γ and MCP-1 in EV71-infected RD cells. Altogether, these results revealed that CHA may have antiviral properties for treating EV71 infection.

Highlights

Enteroviruses belong to the family Picornaviridae, which has >70 serotypes including poliovirus, coxsackievirus A (A1-22 and A24), coxsackievirus B (B1–6), echovirus (1–21 and 24–33) and enterovirus (68–71, 73–78 and 89–91) [1,2]
To delineate whether the inhibitory effects of CHA on Enterovirus 71 (EV71) replication was associated with cytotoxicity, we examined the viability of RD cells after treating with CHA for 5 days
Antiviral effects of CHA against EV71 Our results showed that CHA and ribavirin could significantly inhibit the cytopathic effect of EV71

Summary

Introduction

Enteroviruses belong to the family Picornaviridae, which has >70 serotypes including poliovirus (types 1, 2 and 3), coxsackievirus A (A1-22 and A24), coxsackievirus B (B1–6), echovirus (1–21 and 24–33) and enterovirus (68–71, 73–78 and 89–91) [1,2]. The viral genome is approximately 7,500 nucleotides in length, with a single open reading frame that encodes a large precursor protein [5]. The internal ribosome entry site (IRES) element in the 5’-untranslated region (UTR) initiates the translation of the viral processor polyprotein, which is proteolytically cleaved by viral 2A, 3C and 3D proteases to form four structural (VP1, VP2, VP3, and VP4) and seven nonstructural (2A, 2B, 2C, 3A, 3B, 3C, and 3D) proteins [6]. Viral infections are treated with vaccines, anti-viral synthetic drugs, and exogenous cytokines [7,8,9,10]. Due to multiple viral species and serotype, antigenic variation, and genomic mutations, there is no proven effective treatment for EV71 infection [11]. CHA is the major active ingredient found in many traditional Chinese herbs and herbal medicine [12]

Methods

Results

Conclusion