Lin Shih-Chao, Chen Mei-Chun, Li Shiming, Lin Chi-Chen, Wang Tony T
PhD Program in Medical Biotechnology, National Chung Hsing University, Taichung, Taiwan.
National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, USA.
Antivir Ther. 2017;22(8):689-697. doi: 10.3851/IMP3167.
Chikungunya virus (CHIKV), a highly contagious re-emerging virus, is transmitted by infected mosquitoes. CHIKV is prevalent in tropical countries and is continuing to creep farther north into temperate areas. CHIKV is responsible for induction of chikungunya fever (CF) and severe joint stiffness with the capability of developing into bilateral and systemic arthralgia or even encephalitis. Despite the high morbidity rate, no approved antiviral drug is available. Therefore, an anti-CHIKV therapy is necessary to control this disease. In this study, we screened four flavonoids for anti-CHIKV activities: nobiletin, phlorizin, resveratrol and oxyresveratrol.
We performed MTT, Viral ToxGlo and lactate dehydrogenase (LDH) assays to assess the viability of CHIKV-infected host cells. Plaque assay and immunofluorescent assay were utilized to evaluate the levels of viral production in quantification and qualification, respectively.
We first confirmed that nobiletin can maintain the cellular survival of infected cells without inducing significant toxicity to host cells. Nobiletin suppressed virus-induced cell death and viral production. Also, the antiviral efficacy of nobiletin can last for at least 48 h during infection. More importantly, nobiletin inhibited CHIKV infection during the translation/replication stages and viral entry, making nobiletin a potential clinical antiviral agent in prophylaxis and post-exposure treatment.
In this study, our results provided a strategy to develop anti-chikungunya agents by utilizing natural compounds. Also, we believe that nobiletin can be a potential antiviral agent against CHIKV infection worthy of being further investigated as a remedial candidate in vivo.
基孔肯雅病毒（CHIKV）是一种具有高度传染性的再度出现的病毒，通过受感染的蚊子传播。CHIKV在热带国家流行，并继续向北蔓延至温带地区。CHIKV可引发基孔肯雅热（CF）和严重的关节僵硬，并有发展为双侧和全身性关节痛甚至脑炎的可能。尽管发病率很高，但目前尚无获批的抗病毒药物。因此，有必要开发抗CHIKV疗法来控制这种疾病。在本研究中，我们筛选了四种具有抗CHIKV活性的黄酮类化合物：川陈皮素、根皮苷、白藜芦醇和氧化白藜芦醇。
我们进行了MTT、Viral ToxGlo和乳酸脱氢酶（LDH）测定，以评估CHIKV感染的宿主细胞的活力。分别利用蚀斑测定法和免疫荧光测定法从定量和定性方面评估病毒产生水平。
我们首先证实，川陈皮素可以维持受感染细胞的细胞存活，而不会对宿主细胞产生明显毒性。川陈皮素可抑制病毒诱导的细胞死亡和病毒产生。此外，川陈皮素的抗病毒功效在感染期间可持续至少48小时。更重要的是，川陈皮素在翻译/复制阶段和病毒进入过程中抑制CHIKV感染，这使得川陈皮素成为预防和暴露后治疗中潜在的临床抗病毒药物。
在本研究中，我们的结果提供了一种利用天然化合物开发抗基孔肯雅病毒药物的策略。此外，我们认为川陈皮素可能是一种抗CHIKV感染的潜在抗病毒药物，值得作为体内治疗候选药物进一步研究。
