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锌盐和镁盐抗基孔肯雅病毒的抗病毒潜力研究:治疗意义。

Explorations on the antiviral potential of zinc and magnesium salts against chikungunya virus: implications for therapeutics.

机构信息

Dengue and Chikungunya Group, ICMR-National Institute of Virology, Pune, India.

Bioinformatics Group, ICMR-National Institute of Virology, Pune, India.

出版信息

Front Cell Infect Microbiol. 2024 Jun 4;14:1335189. doi: 10.3389/fcimb.2024.1335189. eCollection 2024.

DOI:10.3389/fcimb.2024.1335189
PMID:38895735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11183322/
Abstract

BACKGROUND

Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of patients develop chronic arthritis after an infection. Zinc and magnesium salts help the immune system respond effectively against viral infections. This study explored the antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV infection.

METHODS

The highest non-toxic concentration of the salts (100 µM) was used to assess the prophylactic, virucidal, and therapeutic anti-CHIKV activities. Dose-dependent antiviral effects were investigated to find out the 50% inhibitory concentration of the salts. Entry bypass assay was conducted to find out whether the salts affect virus entry or post entry stages. Virus output in all these experiments was estimated using a focus-forming unit assay, real-time RT-PCR, and immunofluorescence assay.

RESULTS

Different time- and temperature-dependent assays revealed the therapeutic antiviral activity of zinc and magnesium salts against CHIKV. A minimum exposure of 4 hours and treatment initiation within 1 to 2 hours of infection are required for inhibition of CHIKV. Entry assays revealed that zinc salt affected virus-entry. Entry bypass assays suggested that both salts affected post-entry stages of CHIKV. In infected C57BL6 mice orally fed with zinc and magnesium salts, a reduction in viral RNA copy number was observed.

CONCLUSION

The study results suggest zinc salts exert anti-CHIKV activity at entry and post entry stages of the virus life cycle, while magnesium salt affect CHIKV at post entry stages. Overall, the study highlights the significant antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV, which can be exploited in designing potential therapeutic strategies for early treatment of chikungunya patients, thereby reducing the virus-associated persistent arthritis.

摘要

背景

基孔肯雅病毒(CHIKV)引起基孔肯雅热,是一种具有公共卫生意义的虫媒病毒,目前尚无批准的抗病毒疗法。很大一部分患者在感染后会发展为慢性关节炎。锌盐和镁盐有助于免疫系统有效抵抗病毒感染。本研究探讨了硫酸锌、醋酸锌和硫酸镁对 CHIKV 感染的抗病毒潜力。

方法

使用最高无毒浓度(100µM)的盐来评估盐的预防、杀病毒和治疗抗 CHIKV 活性。进行剂量依赖性抗病毒作用研究,以确定盐的 50%抑制浓度。进行进入旁路测定,以确定盐是否影响病毒进入或进入后阶段。在所有这些实验中,使用焦点形成单位测定、实时 RT-PCR 和免疫荧光测定来估计病毒产量。

结果

不同的时间和温度依赖性测定显示锌和镁盐对 CHIKV 具有治疗性抗病毒活性。需要至少 4 小时的暴露和在感染后 1 至 2 小时内开始治疗才能抑制 CHIKV。进入测定显示锌盐影响病毒进入。进入旁路测定表明两种盐都影响 CHIKV 的进入后阶段。在感染 C57BL6 小鼠中经口给予锌和镁盐,观察到病毒 RNA 拷贝数减少。

结论

研究结果表明,锌盐在病毒生命周期的进入和进入后阶段发挥抗 CHIKV 活性,而镁盐在进入后阶段影响 CHIKV。总的来说,该研究强调了硫酸锌、醋酸锌和硫酸镁对 CHIKV 的显著抗病毒潜力,可用于设计针对早期治疗基孔肯雅患者的潜在治疗策略,从而减少与病毒相关的持续性关节炎。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/c61c16ccc342/fcimb-14-1335189-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/631d7f0fd671/fcimb-14-1335189-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/5ea890690552/fcimb-14-1335189-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/8120338aca70/fcimb-14-1335189-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/5d585602a359/fcimb-14-1335189-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/3762b398e4f1/fcimb-14-1335189-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/830cecae08df/fcimb-14-1335189-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/c61c16ccc342/fcimb-14-1335189-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/631d7f0fd671/fcimb-14-1335189-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/5ea890690552/fcimb-14-1335189-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/8120338aca70/fcimb-14-1335189-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/5d585602a359/fcimb-14-1335189-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/3762b398e4f1/fcimb-14-1335189-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/830cecae08df/fcimb-14-1335189-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5047/11183322/c61c16ccc342/fcimb-14-1335189-g007.jpg

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