Identification of surfactin as an anti-severe fever with thrombocytopenia syndrome virus multi-target compound extracted from the culture broth of marine microbes
Identification of surfactin as an anti-severe fever with thrombocytopenia syndrome virus multi-target compound extracted from the culture broth of marine microbes
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DOI：
10.3389/fviro.2022.1064265
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
Shuzo Urata;Jun Takouda;Yoshihiro Watanabe;M. Sakaguchi;Yasuteru Sakurai;Yuki Inahashi;M. Iwatsuki;J. Yasuda;Yoshimasa Tanaka;K. Takeda
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文献类型：
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作者：
Shuzo Urata;Jun Takouda;Yoshihiro Watanabe;M. Sakaguchi;Yasuteru Sakurai;Yuki Inahashi;M. Iwatsuki;J. Yasuda;Yoshimasa Tanaka;K. Takeda
严重发热伴血小板减少综合征病毒是2011年在中国首次发现的一种硬蜱传播病毒，后来在其他亚洲国家和地区报告。已经做出了重大努力来开发抗猪瘟病毒的化合物；然而，还没有批准的针对猪瘟病毒感染的疫苗或抗病毒药物。海洋生物为生产治疗和控制疾病的治疗药物提供了几乎无限的生物资源。在这项研究中，我们的目的是从日本长崎县沿海采集的海洋微生物培养液萃取物中鉴定抗SFTSV的化合物。在80个提取物中，有两个提取物显示出抗SFTSV的作用。其中一种表现出较低的细胞毒性，用于进一步的表征。化学分析结合抗SFTSV作用，确定表面活性物质为所选提取物的主要成分之一。我们的研究显示了一种概念验证，可以从海洋微生物中鉴定出针对感兴趣病毒的新型抗病毒化合物。进一步分析表明，在低pH条件下，表面蛋白影响病毒粒子膜的完整性，并抑制SFTSV感染诱导的膜融合。此外，表面蛋白抑制病毒进入细胞后的复制步骤，这是表面蛋白抗病毒作用的一种新模式。这些结果表明，表面蛋白可以靶向细胞内多个步骤的SFTSV复制。
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus first identified in China in 2011 and later reported in other Asian countries. Significant efforts have been made to develop anti-SFTSV compounds; however, there are no approved vaccines or antivirals against SFTSV infections. Marine organisms provide nearly unlimited biological resources to produce therapeutic drugs for the treatment and control of disease. In this study, we aimed to identify anti-SFTSV chemical compounds from the culture broth extracts of marine microbes collected from the coasts of the Nagasaki Prefecture, Japan. Of the 80 extracts, two showed an anti-SFTSV effect. One of them, which exhibited low cell toxicity, was used for further characterization. Chemical analysis combined with the anti-SFTSV effect identified surfactin as one of the main components of the selected extract. Our study showed a proof-of-concept to identify novel antiviral compounds from marine microbes against the virus of interest. Further analysis showed that surfactin affected the integrity of the virion membrane and inhibited SFTSV infection-induced membrane fusion at low pH conditions. Furthermore, surfactin inhibits the post-entry step of viral replication in the cell, which is a novel mode of antiviral action of surfactin. These results indicate that surfactin can target multiple steps of SFTSV replication in cells.