Caffeic acid, a coffee-related organic acid, inhibits infection by severe fever with thrombocytopenia syndrome virus in vitro
Caffeic acid, a coffee-related organic acid, inhibits infection by severe fever with thrombocytopenia syndrome virus in vitro
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DOI：
10.1016/j.jiac.2018.03.005
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发表时间：
2018-08-01
影响因子：
2.2
通讯作者：
Fukasawa, Masayoshi
中科院分区：
文献类型：
--
作者：
Ogawa, Motohiko;Shirasago, Yoshitaka;Fukasawa, Masayoshi
严重发热伴血小板减少综合征(SFTS)病毒(SFTSV)可在东亚引起硬蜱传播的出血热。该病的特点是发病率和死亡率高。在这里，我们评估了咖啡酸(CA)，一种与咖啡相关的具有抗病毒作用的有机酸，对SFTSV感染的影响。在含有CA的培养液中加入SFTSV后，CA呈剂量依赖性地抑制人肝癌细胞株Huh7.5.1-8的SFTSV感染。然而，另一种与咖啡相关的有机酸奎尼酸(QA)并不能抑制SFTSV的感染。CA对烟草花叶病毒的半数抑制浓度(IC50)为0.048 mM，半数细胞毒浓度(IC50)为7.6 mM。选择性指数(SI)为158。猪瘟病毒与CA预先孵育4h，对猪瘟病毒的感染有较强的抑制作用(IC_(50)=0.019 mm；SI=400)。预孵化大大减少了病毒对细胞的附着。CA处理受SFTSV感染的细胞也抑制了感染，尽管效果较差。在低感染复数(MOI)为0.01个/细胞(IC50=0.18 mm)的情况下，细胞感染SFTSV后的CA活性比高MOI为1个/细胞(IC50和GT；1 mm)时更为明显。因此，CA通过直接作用于病毒而不是作用于受感染的细胞来抑制病毒传播。综上所述，CA作用于SFTSV，主要通过抑制SFTSV与细胞的结合，从而抑制病毒的感染和传播。因此，我们证明了CA是一种潜在的预防和治疗SFTS的抗SFTSV药物。(C)2018年日本化疗学会和日本传染病协会。爱思唯尔有限公司出版。保留所有权利。
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) causes tick-borne hemorrhagic fever in East Asia. The disease is characterized by high morbidity and mortality. Here, we evaluated the effects of caffeic acid (CA), a coffee-related organic acid with antiviral effects, against SFTSV infection. CA dose-dependently inhibited SFTSV infection in permissive human hepatoma Huh7.5.1-8 cells when SFTSV was added into the culture medium with CA. However, quinic acid (QA), another coffee-related organic acid, did not inhibit SFTSV infection. The 50% inhibitory concentration (IC50) of CA against SFTSV was 0.048 mM, whereas its 50% cytotoxic concentration was 7.6 mM. The selectivity index (SI) was 158. Pre-incubation of SFTSV with CA for 4 h resulted in a greater inhibition of SFTSV infection (IC50 = 0.019 mM; SI = 400). The pre-incubation substantially decreased viral attachment to the cells. CA treatment of the SFTSV-infected cells also inhibited the infection, albeit less effectively. CA activity after cell infection with SFTSV was more pronounced at a low multiplicity of infection (MOI) of 0.01 per cell (IC50 = 0.18 mM) than at a high MOI of 1 per cell (IC50 > 1 mM). Thus, CA inhibited virus spread by acting directly on the virus rather than on the infected cells. In conclusion, CA acted on SFTSV and inhibited viral infection and spread, mainly by inhibiting the binding of SFTSV to the cells. We therefore demonstrated CA to be a potential anti-SFTSV drug for preventing and treating SFTS. (C) 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.