A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection.
A Novel Sphingosine Kinase Inhibitor Suppresses Chikungunya Virus Infection.
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DOI：
10.3390/v14061123
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发表时间：
2022-05-24
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基孔肯雅病毒（CHIKV）是甲病毒属中重新出现的虫媒病毒。一旦感染，它会导致严重的关节疼痛，在一些患者中可能持续数年，严重影响他们的生活质量。目前，没有针对CHIKV的疫苗或抗病毒疗法。它从东部大陆传播到美洲，使感染者人数大大增加了数百万。因此，迫切需要鉴定用于CHIKV治疗的治疗靶标。一个潜在的干预点是鞘氨醇-1-磷酸（S1 P）途径。鞘氨醇转化为S1 P是由鞘氨醇激酶（SK）催化的，我们先前表明其在CHIKV感染期间是关键的前病毒宿主因子。在这项研究中，我们筛选了SK的抑制剂，并确定了一种新的有效的CHIKV感染抑制剂-SLL 3071511。我们发现，在预防和治疗模式下，用SLL 3071511体外预处理细胞有效抑制了CHIKV感染，EC 50值为2.91 µM，显著降低了病毒基因表达和病毒颗粒的释放。我们的研究表明，靶向SK是控制CHIKV复制的可行方法。
Chikungunya virus (CHIKV) is a re-emerging arbovirus in the alphavirus genus. Upon infection, it can cause severe joint pain that can last years in some patients, significantly affecting their quality of life. Currently, there are no vaccines or anti-viral therapies available against CHIKV. Its spread to the Americas from the eastern continents has substantially increased the count of the infected by millions. Thus, there is an urgent need to identify therapeutic targets for CHIKV treatment. A potential point of intervention is the sphingosine-1-phosphate (S1P) pathway. Conversion of sphingosine to S1P is catalyzed by Sphingosine kinases (SKs), which we previously showed to be crucial pro-viral host factor during CHIKV infection. In this study, we screened inhibitors of SKs and identified a novel potent inhibitor of CHIKV infection—SLL3071511. We showed that the pre-treatment of cells with SLL3071511 in vitro effectively inhibited CHIKV infection with an EC50 value of 2.91 µM under both prophylactic and therapeutic modes, significantly decreasing the viral gene expression and release of viral particles. Our studies suggest that targeting SKs is a viable approach for controlling CHIKV replication.
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DOI：
10.1126/science.1176709
发表时间：
2009-09-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Spiegel S
DOI：
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发表时间：
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影响因子：
3.5
作者：
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Lynch, Kevin R.
影响因子：
56.9
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通讯作者：
Santos WL