Please use this identifier to cite or link to this item: https://doi.org/10.1128/AAC.01467-12
Title: Inhibition of Chikungunya Virus Replication by Harringtonine, a Novel Antiviral That Suppresses Viral Protein Expression
Authors: Kaur, Parveen
Thiruchelvan, Meerra
Lee, Regina Ching Hua
Chen, Huixin 
Chen, Karen Caiyun
Ng, Mah Lee 
Chu, Justin Jang Hann 
Keywords: Aedes
Animals
Antiviral Agents
Biological Products
Cell Line
Chikungunya virus
Cricetinae
Dose-Response Relationship, Drug
Fluorescent Antibody Technique
Gene Expression
Harringtonines
High-Throughput Screening Assays
Humans
Protein Biosynthesis
RNA, Viral
Sindbis Virus
Small Molecule Libraries
Transduction, Genetic
Virus Replication
Issue Date: Jan-2013
Publisher: American Society for Microbiology
Citation: Kaur, Parveen, Thiruchelvan, Meerra, Lee, Regina Ching Hua, Chen, Huixin, Chen, Karen Caiyun, Ng, Mah Lee, Chu, Justin Jang Hann (2013-01). Inhibition of Chikungunya Virus Replication by Harringtonine, a Novel Antiviral That Suppresses Viral Protein Expression. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 57 (1) : 155-167. ScholarBank@NUS Repository. https://doi.org/10.1128/AAC.01467-12
Abstract: Chikungunya virus (CHIKV) is a mosquito-transmitted virus that has reemerged as a significant public health threat in the last decade. Since the 2005-2006 chikungunya fever epidemic in the Indian Ocean island of La Réunion, millions of people in more than 40 countries have been infected. Despite this, there is currently no antiviral treatment for chikungunya infection. In this study, an immunofluorescence-based screening platform was developed to identify potential inhibitors of CHIKV infection. A primary screen was performed using a highly purified natural product compound library, and 44 compounds exhibiting ≥70% inhibition of CHIKV infection were identified as positive hits. Among these, four were selected for dose-dependent inhibition assays to confirm their anti-CHIKV activity. Harringtonine, a cephalotaxine alkaloid, displayed potent inhibition of CHIKV infection (50% effective concentration [EC50] = 0.24 μM) with minimal cytotoxicity and was selected for elucidation of its antiviral mechanism. Time-of-addition studies, cotreatment assays, and direct transfection of viral genomic RNA indicated that harringtonine inhibited an early stage of the CHIKV replication cycle which occurred after viral entry into cells. In addition, quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses indicated that harringtonine affects CHIKV RNA production as well as viral protein expression. Treatment of harringtonine against Sindbis virus, a related alphavirus, suggested that harringtonine could inhibit other alphaviruses. This study suggests for the first time that harringtonine exerts its antiviral effects by inhibiting CHIKV viral protein synthesis. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
Source Title: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
URI: https://scholarbank.nus.edu.sg/handle/10635/173293
ISSN: 00664804
10986596
DOI: 10.1128/AAC.01467-12
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