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Antiviral activity of stearylamine against chikungunya virus
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2021-01-07 , DOI: 10.1016/j.chemphyslip.2021.105049
Manish Kumar Jeengar 1 , Mallesh Kurakula 2 , Poonam Patil 1 , Ashwini More 1 , Ramakrishna Sistla 2 , Deepti Parashar 1
Affiliation  

Chikungunya, a mosquito-borne disease that causes high fever and severe joint pain in humans, is a profound global threat because of its high rate of contagion and lack of antiviral interventions or vaccines for controlling the infection. The present study was aimed to investigate the antiviral activity of Stearylamine (SA) against Chikungunya virus (CHIKV) in both in vitro and in vivo. The antiviral activity of SA was determined by foci forming unit (FFU) assay, quantitative RT-PCR and cell-based immune-fluorescence assay (IFA). Further in vivo studies were carried out to see the effect of SA treatment in CHIKV infected C57BL/6 mice. The anti-CHIKV activity was evaluated using qRT-PCR in serum and muscle tissues at different time points and by histopathology. In vitro treatment with SA at a concentration of 50 μM showed a reduction of 1.23 ± 0.19 log10 FFU/mL at 16 h and 1.56 ± 0.12 log10 FFU/mL at 24 h posttreatment by FFU assay. qRT-PCR studies indicated that SA treatment at 50μM concentration showed a singnificant reduction of 1.6 ± 0.1 log10 and 1.27 ± 0.12 log10 RNA copies when compared with that of virus control at 16 and 24 h post incubation. Treatments in the C57BL/6 mice model revealed that SA at 20 mg/kg dose per day up to 3, 5 and 7 days, produced stronger inhibition against CHIKV indicating substantially decrease viral loads and inflammatory cell migration in comparison to a dose of 10 mg/kg. This first in vivo study clearly indicates that SA is effective by significantly reducing virus replication in serum and muscles. As a next-generation antiviral therapeutic, these promising results can be translated for the use of SA to rationalize and develop an ideal delivery system alone or in combination against CHIKV.



中文翻译:

硬脂胺对基孔肯雅病毒的抗病毒活性

基孔肯雅热是一种由蚊子传播的疾病,会导致人类高烧和严重的关节疼痛,由于其高传染率和缺乏控制感染的抗病毒干预措施或疫苗,它是一个深刻的全球威胁。本研究的目的是在这两个调查硬脂胺(SA)对基孔肯雅病毒(CHIKV)的抗病毒活性体外体内。SA的抗病毒活性通过病灶形成单位(FFU)测定、定量RT-PCR和基于细胞的免疫荧光测定(IFA)测定。进一步体内进行了研究以观察 SA 治疗对 CHIKV 感染的 C57BL/6 小鼠的影响。使用 qRT-PCR 在不同时间点的血清和肌肉组织中并通过组织病理学评估抗 CHIKV 活性。体外通过 FFU 测定,用 50 μM 浓度的 SA 处理显示在 16 小时和 24 小时后降低 1.23 ± 0.19 log10 FFU/mL 和 1.56 ± 0.12 log10 FFU/mL。qRT-PCR 研究表明,与病毒对照在孵育后 16 小时和 24 小时相比,50μM 浓度的 SA 处理显示出 1.6 ± 0.1 log10 和 1.27 ± 0.12 log10 RNA 拷贝的显着减少。在 C57BL/6 小鼠模型中的治疗表明,每天 20 毫克/千克剂量的 SA 持续 3、5 和 7 天,对 CHIKV 产生更强的抑制,表明与 10 毫克剂量相比,病毒载量和炎症细胞迁移显着降低/公斤。这首先在体内研究清楚地表明 SA 通过显着减少血清和肌肉中的病毒复制而有效。作为下一代抗病毒疗法,这些有希望的结果可以转化为使用 SA 来合理化和开发理想的单独或组合对抗 CHIKV 的递送系统。

更新日期:2021-01-22
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