Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Int J Biol Sci. 2010 May 23;6(3):294-302. doi: 10.7150/ijbs.6.294.
Dengue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever and its associated complications, dengue haemorrhagic fever and dengue shock syndrome. To date, more than 2.5 billion people in over 100 countries are at risk of infection, and approximately 20 million infections were reported annually. There is currently no treatment or vaccine available for dengue infection. This study employed a whole-cell organism model or in vitro methods to study the inhibitory property of the flavanoid-derived compounds against DENV2 activity. Results showed that at concentration not exceeding the maximum non-toxic dose (MNTD), these compounds completely prevented DENV2 infection in HepG2 cells as indicated by the absence of cytophatic effects. The in vitro antiviral activity assessed in HepG2 cells employing virus inhibition assay showed high inhibitory activity in a dose dependent manner. At concentration below MNTD, compounds exhibited inhibitory activity against DENV2 with a range of potency strengths of 72% to 100%. The plaque forming unit per ml (pfu/ml) was reduced prominently with a maximum reduction of 98% when the infected HepG2 cells were treated with the highest non-toxic dose of compounds. The highly potent activity of the compounds against DENV2 infection strongly suggests their potential as a lead antiviral agent for dengue.
登革热病毒属于黄病毒科,通过蚊子传播,是登革热及其相关并发症(登革出血热和登革休克综合征)的病原体。迄今为止,全世界有超过 100 个国家的 25 亿多人面临感染风险,每年报告的感染人数约为 2000 万。目前,尚无针对登革热感染的治疗方法或疫苗。本研究采用全细胞生物模型或体外方法研究了类黄酮衍生化合物对 DENV2 活性的抑制特性。结果表明,在不超过最大无毒剂量 (MNTD) 的浓度下,这些化合物完全阻止了 HepG2 细胞中的 DENV2 感染,因为没有出现细胞病变效应。在 HepG2 细胞中使用病毒抑制测定法评估的体外抗病毒活性表现出剂量依赖性的高抑制活性。在 MNTD 以下的浓度下,化合物对 DENV2 表现出抑制活性,效力范围为 72%至 100%。当用化合物的最高无毒剂量处理感染的 HepG2 细胞时,每毫升空斑形成单位(pfu/ml)明显减少,最大减少 98%。这些化合物对 DENV2 感染的高度有效活性强烈表明它们具有作为登革热潜在的先导抗病毒药物的潜力。