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金精三羧酸对寨卡病毒复制的强效抑制作用

Potent Inhibition of Zika Virus Replication by Aurintricarboxylic Acid.

作者信息

Park Jun-Gyu, Ávila-Pérez Ginés, Madere Ferralita, Hilimire Thomas A, Nogales Aitor, Almazán Fernando, Martínez-Sobrido Luis

机构信息

Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, United States.

Center for Animal Health Research, INIA-CISA, Madrid, Spain.

出版信息

Front Microbiol. 2019 Apr 12;10:718. doi: 10.3389/fmicb.2019.00718. eCollection 2019.

DOI:10.3389/fmicb.2019.00718
PMID:31031722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6473159/
Abstract

Zika virus (ZIKV) is one of the recently emerging vector-borne viruses in humans and is responsible for severe congenital abnormalities such as microcephaly in the Western Hemisphere. Currently, only a few vaccine candidates and therapeutic drugs are being developed for the treatment of ZIKV infections, and as of yet none are commercially available. The polyanionic aromatic compound aurintricarboxylic acid (ATA) has been shown to have a broad-spectrum antimicrobial and antiviral activity. In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication showed median inhibitory concentrations (IC) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC) > 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted in effective suppression of ZIKV replication with similar IC. Importantly, the inhibitory effect of ATA on ZIKV infection was effective against strains of the African and Asian/American lineages, indicating that this inhibitory effect was not strain dependent. Overall, these results demonstrate that ATA has potent inhibitory activity against ZIKV replication and may be considered as a potential anti-ZIKV therapy for future clinical evaluation.

摘要

寨卡病毒（ZIKV）是人类中最近出现的虫媒病毒之一，在西半球导致了如小头畸形等严重的先天性异常。目前，仅有少数候选疫苗和治疗药物正在研发用于治疗寨卡病毒感染，且尚无任何一种可供商业使用。聚阴离子芳香族化合物金精三羧酸（ATA）已被证明具有广谱抗菌和抗病毒活性。在本研究中，我们评估了ATA作为一种抗寨卡病毒复制的潜在抗病毒药物。ATA对寨卡病毒复制的抗病毒活性在Vero细胞和A549细胞中的半数抑制浓度（IC）分别为13.87±1.09μM和33.33±1.13μM；在两种细胞系中均未显示出任何细胞毒性作用（半数细胞毒性浓度（CC）>1000μM）。此外，ATA以时间和浓度依赖性方式保护两种细胞类型免受寨卡病毒诱导的细胞病变效应（CPE）和凋亡。另外，用ATA预处理Vero细胞长达72小时也导致以相似的IC有效抑制寨卡病毒复制。重要的是，ATA对寨卡病毒感染的抑制作用对非洲和亚洲/美洲谱系的毒株均有效，表明这种抑制作用不依赖于毒株。总体而言，这些结果表明ATA对寨卡病毒复制具有强大的抑制活性，可被视为未来临床评估的潜在抗寨卡病毒疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/9dca4cef59dd/fmicb-10-00718-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/c2213335bf56/fmicb-10-00718-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/baba64218c90/fmicb-10-00718-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/8f07b95e72bd/fmicb-10-00718-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/9dca4cef59dd/fmicb-10-00718-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/c2213335bf56/fmicb-10-00718-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/3aa84df2a2cf/fmicb-10-00718-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/e73c88f3ee00/fmicb-10-00718-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/f1110bc5e335/fmicb-10-00718-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/8f07b95e72bd/fmicb-10-00718-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cae/6473159/9dca4cef59dd/fmicb-10-00718-g007.jpg

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