Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells.

Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells.
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DOI:
10.3390/molecules26113118
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发表时间:
2021-05-23
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Yenchitsomanus PT
Yenchitsomanus PT
中科院分区:
其他
文献类型:
--
作者:
Panya A;Songprakhon P;Panwong S;Jantakee K;Kaewkod T;Tragoolpua Y;Sawasdee N;Lee VS;Nimmanpipug P;Yenchitsomanus PT

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登革病毒(DENV)感染导致人类轻度至重度疾病,严重病例可导致死亡。目前,没有特定的药物可用于治疗DENV感染。因此,迫切需要开发抗DENV药物。虫草素(Cordycepin,3′-deoxyadenosine)是虫草(Cordyceps,Ascomycete)真菌中的一种重要生物活性物质,具有抗病毒活性。然而,虫草素的抗DENV活性是未知的。我们假设虫草素具有抗DENV活性,并且作为腺苷衍生物,它抑制DENV复制。为了验证这一假设,我们研究了虫草素在DENV感染的Vero细胞中的抗DENV活性。虫草素处理显著降低DENV蛋白,半数最大有效浓度(EC 50)为26.94 μM。此外,在虫草素处理的Vero细胞中,DENV RNA显著减少,表明其在抑制病毒RNA复制方面的有效性。通过计算机分子对接,预测了虫草素与登革病毒非结构蛋白5(NS 5)在甲基转移酶(MTase)和RNA依赖性RNA聚合酶(RdRp)两个结构域的结合。本研究的结果表明,虫草素能够抑制登革病毒的复制,这预示着其作为抗登革治疗的潜力。
Dengue virus (DENV) infection causes mild to severe illness in humans that can lead to fatality in severe cases. Currently, no specific drug is available for the treatment of DENV infection. Thus, the development of an anti-DENV drug is urgently required. Cordycepin (3′-deoxyadenosine), which is a major bioactive compound in Cordyceps (ascomycete) fungus that has been used for centuries in Chinese traditional medicine, was reported to exhibit antiviral activity. However, the anti-DENV activity of cordycepin is unknown. We hypothesized that cordycepin exerts anti-DENV activity and that, as an adenosine derivative, it inhibits DENV replication. To test this hypothesis, we investigated the anti-DENV activity of cordycepin in DENV-infected Vero cells. Cordycepin treatment significantly decreased DENV protein at a half-maximal effective concentration (EC50) of 26.94 μM. Moreover, DENV RNA was dramatically decreased in cordycepin-treated Vero cells, indicating its effectiveness in inhibiting viral RNA replication. Via in silico molecular docking, the binding of cordycepin to DENV non-structural protein 5 (NS5), which is an important enzyme for RNA synthesis, at both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, was predicted. The results of this study demonstrate that cordycepin is able to inhibit DENV replication, which portends its potential as an anti-dengue therapy.
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