关键词: antiviral agents chikungunya virus magnesium therapeutics zinc

Mesh : Chikungunya virus / drug effects Animals Antiviral Agents / pharmacology therapeutic use Chikungunya Fever / drug therapy virology Zinc Acetate / pharmacology therapeutic use Zinc Sulfate / pharmacology Chlorocebus aethiops Vero Cells Virus Internalization / drug effects Mice Zinc / pharmacology therapeutic use Humans Magnesium Sulfate / pharmacology Magnesium / pharmacology Virus Replication / drug effects Inhibitory Concentration 50 Salts / pharmacology Cell Line

来  源:   DOI:10.3389/fcimb.2024.1335189   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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:
基孔肯雅病毒(CHIKV),导致基孔肯雅热,是一种公共卫生问题的虫媒病毒,没有批准的抗病毒疗法。相当比例的患者在感染后发展为慢性关节炎。锌和镁盐帮助免疫系统有效地应对病毒感染。这项研究探索了硫酸锌的抗病毒潜力,醋酸锌,和硫酸镁对抗CHIKV感染.
盐的最高无毒浓度(100µM)用于评估预防剂,杀病毒,和治疗性抗CHIKV活动。研究剂量依赖性抗病毒作用以找出盐的50%抑制浓度。进行进入旁路测定以查明盐是否影响病毒进入或进入后阶段。所有这些实验中的病毒输出都是使用焦点形成单位测定来估计的,实时RT-PCR,和免疫荧光分析。
不同的时间和温度依赖性测定揭示了锌盐和镁盐对CHIKV的治疗性抗病毒活性。抑制CHIKV需要最少4小时的暴露和在感染后1至2小时内开始治疗。进入测定显示锌盐影响病毒进入。进入旁路实验表明,两种盐都会影响CHIKV的进入后阶段。在口服锌和镁盐的感染C57BL6小鼠中,观察到病毒RNA拷贝数减少.
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会影响CHIKV。总的来说,这项研究强调了硫酸锌的巨大抗病毒潜力,醋酸锌,和硫酸镁对抗CHIKV,可用于设计基孔肯雅患者早期治疗的潜在治疗策略,从而减少病毒相关的持续性关节炎。
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