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探索阿昔洛韦对蛙病毒胸苷激酶的有效性:在鱼类细胞系中的分子对接和实验验证

Exploring the Effectiveness of Acyclovir against Ranaviral Thymidine Kinases: Molecular Docking and Experimental Validation in a Fish Cell Line.

作者信息

Rácz Richárd, Gellért Ákos, Papp Tibor, Doszpoly Andor

机构信息

HUN-REN Veterinary Medical Research Institute, H-1143 Budapest, Hungary.

出版信息

Life (Basel). 2024 Aug 23;14(9):1050. doi: 10.3390/life14091050.

DOI:10.3390/life14091050
PMID:39337837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11433535/
Abstract

The effectiveness of acyclovir, a selective anti-herpesvirus agent, was tested both in silico and in vitro against two ranaviruses, namely the European catfish virus (ECV) and Frog virus 3 (FV3). ECV can cause significant losses in catfish aquaculture, while FV3 poses a risk to vulnerable amphibian populations. The genome of ranaviruses encodes thymidine kinases (TKs) similar to those of herpesviruses. Molecular docking simulations demonstrated that the acyclovir molecule can bind to the active sites of both investigated viral TKs in an orientation conducive to phosphorylation. Subsequently, the antiviral effect of acyclovir was tested in vitro in Epithelioma Papulosum Cyprini (EPC) cells with endpoint titration and qPCR. Acyclovir was used at a concentration of 800 µM, which significantly reduced the viral loads and titers of the ranaviruses. A similar reduction rate was observed with Ictalurid herpesvirus 2, which was used as a positive control virus. These promising results indicate that acyclovir might have a wider range of uses; besides its effectiveness against herpesviruses, it could also be used against ranavirus infections.

摘要

阿昔洛韦是一种选择性抗疱疹病毒药物,其有效性在计算机模拟和体外实验中针对两种蛙病毒进行了测试,这两种蛙病毒分别是欧洲鲶鱼病毒(ECV)和蛙病毒3型(FV3)。ECV可在鲶鱼养殖中造成重大损失,而FV3对易受影响的两栖动物种群构成风险。蛙病毒的基因组编码与疱疹病毒相似的胸苷激酶(TKs)。分子对接模拟表明,阿昔洛韦分子能够以有利于磷酸化的方向结合到两种被研究病毒TKs的活性位点上。随后,通过终点滴定和qPCR在鲤上皮瘤(EPC)细胞中对阿昔洛韦的抗病毒效果进行了体外测试。阿昔洛韦的使用浓度为800µM,这显著降低了蛙病毒的病毒载量和滴度。作为阳性对照病毒的斑点叉尾鮰疱疹病毒2也观察到了类似的降低率。这些有前景的结果表明,阿昔洛韦可能具有更广泛的用途;除了对疱疹病毒有效外,它还可用于对抗蛙病毒感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/4c4b87e29b12/life-14-01050-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/1047d179aa10/life-14-01050-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/91a5bd84dabf/life-14-01050-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/1d70716b7dd9/life-14-01050-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/4c4b87e29b12/life-14-01050-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/1047d179aa10/life-14-01050-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/91a5bd84dabf/life-14-01050-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/1d70716b7dd9/life-14-01050-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a511/11433535/4c4b87e29b12/life-14-01050-g004.jpg

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本文引用的文献

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Antiviral Chemotherapy in Avian Medicine-A Review.禽医学中的抗病毒化疗——综述
Viruses. 2024 Apr 12;16(4):593. doi: 10.3390/v16040593.
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Silver Nanoparticles Proved to Be Efficient Antivirals In Vitro against Three Highly Pathogenic Fish Viruses.体外实验证明,纳米银颗粒对三种高致病性鱼类病毒具有高效的抗病毒活性。
Viruses. 2023 Aug 3;15(8):1689. doi: 10.3390/v15081689.
3
Efficacy of a multidose acyclovir protocol against cyprinid herpesvirus 3 infection in koi (Cyprinus carpio).多剂量阿昔洛韦方案对锦鲤疱疹病毒 3 感染的疗效(鲤鱼)。
Am J Vet Res. 2022 Nov 4;83(12):ajvr.22.02.0030. doi: 10.2460/ajvr.22.02.0030.
4
Juvenile Wels Catfish () Display Age-Related Mortality to European Catfish Virus (ECV) under Experimental Conditions.幼龄斑点叉尾鮰对欧洲鲶鱼病毒(ECV)在实验条件下表现出与年龄相关的死亡率。
Viruses. 2022 Aug 21;14(8):1832. doi: 10.3390/v14081832.
5
PharmGKB summary: acyclovir/ganciclovir pathway.药物基因组学知识库总结:阿昔洛韦/更昔洛韦途径。
Pharmacogenet Genomics. 2022 Jul 1;32(5):201-208. doi: 10.1097/FPC.0000000000000474. Epub 2022 May 30.
6
40 Years after the Registration of Acyclovir: Do We Need New Anti-Herpetic Drugs?阿昔洛韦注册 40 年后:我们是否需要新型抗疱疹药物?
Int J Mol Sci. 2022 Mar 22;23(7):3431. doi: 10.3390/ijms23073431.
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Acyclovir inhibits white spot syndrome virus replication in crayfish Procambarus clarkii.阿昔洛韦抑制小龙虾克氏原螯虾中的白斑综合征病毒复制。
Virus Res. 2021 Nov;305:198570. doi: 10.1016/j.virusres.2021.198570. Epub 2021 Sep 20.
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Highly accurate protein structure prediction with AlphaFold.利用 AlphaFold 进行高精度蛋白质结构预测。
Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
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Challenges and Solutions to Viral Diseases of Finfish in Marine Aquaculture.海水养殖中食用鱼病毒性疾病的挑战与解决方案
Pathogens. 2021 May 30;10(6):673. doi: 10.3390/pathogens10060673.
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Virus Res. 2021 Jan 15;292:198249. doi: 10.1016/j.virusres.2020.198249. Epub 2020 Nov 27.