Zanello Paula Rodrigues, Koishi Andrea Cristine, Rezende Júnior Celso de Oliveira, Oliveira Larissa Albuquerque, Pereira Adriane Antonia, de Almeida Mauro Vieira, Duarte dos Santos Claudia Nunes, Bordignon Juliano
Laboratório de Virologia Molecular, Instituto Carlos Chagas, ICC/Fiocruz, 81350-010, Curitiba, PR, Brazil.
Departamento de Química, Universidade Federal de Juiz de Fora, 36036-330, Juiz de Fora, MG, Brazil.
Virol J. 2015 Dec 22;12:223. doi: 10.1186/s12985-015-0443-9.
Dengue is the most prevalent arboviral disease in tropical and sub-tropical areas of the world. The incidence of infection is estimated to be 390 million cases and 25,000 deaths per year. Despite these numbers, neither a specific treatment nor a preventive vaccine is available to protect people living in areas of high risk.
With the aim of seeking a treatment that can mitigate dengue infection, we demonstrated that the quinic acid derivatives known as compound 2 and compound 10 were effective against all four dengue virus serotypes and safe for use in a human hepatoma cell line (Huh7.5). Both compounds were non-virucidal to dengue virus particles and did not interfere with early steps of the dengue virus life cycle, including binding and internalization. Experiments using a replicon system demonstrated that compounds 2 and 10 impaired dengue virus replication in Huh7.5 cells. Additionally, the anti-dengue virus effects of the quinic acid derivatives were preserved in human peripheral blood mononuclear cells.
Taken together, these data suggest that quinic acid derivatives represent a novel chemical class of active compounds that could be used to combat dengue virus infection.
登革热是世界热带和亚热带地区最普遍的虫媒病毒病。据估计,每年感染病例达3.9亿例,死亡2.5万人。尽管有这些数据,但尚无特异性治疗方法或预防性疫苗可保护高危地区的人群。
为了寻找能够减轻登革热感染的治疗方法,我们证明了被称为化合物2和化合物10的奎尼酸衍生物对所有四种登革热病毒血清型均有效,并且在人肝癌细胞系(Huh7.5)中使用安全。这两种化合物对登革热病毒颗粒无杀病毒作用,且不干扰登革热病毒生命周期的早期步骤,包括结合和内化。使用复制子系统进行的实验表明,化合物2和10可损害Huh7.5细胞中的登革热病毒复制。此外,奎尼酸衍生物的抗登革热病毒作用在人外周血单核细胞中得以保留。
综上所述,这些数据表明奎尼酸衍生物代表了一类新型的活性化合物,可用于对抗登革热病毒感染。