摘要
Rotavirus is the most common etiologic agent of severe diarrhea in infants and young children and causes more than 200,000 deaths annually worldwide[1,2].Licensed rotavirus vaccines can provide more than 50%protection against rotavirus infection,and currently available etiological treatments for rotavirus gastroenteritis mainly involve the use of oral rehydration solution and zinc supplementation[3].However,targeted interventions are in great need for rotavirus-induced gastroenteritis control.
轮状病毒是全球范围内导致5岁以下儿童严重腹泻的病原物之一.虽然已通过审批的数个轮状病毒疫苗可以保护50%以上的人群免受轮状病毒侵害,现有的轮状病毒腹泻对症治疗手段主要是补锌和补充水分,还急需针对轮状病毒腹泻的特异性靶向治疗手段以快速缓解病人的痛苦.以大规模药物筛选为手段,我们发现dyngo-4a,一个发动蛋白2(dynamin 2)的抑制剂,可以显著抑制轮状病毒感染导致的细胞病变.而且dyngo-4a还可以抑制轮状病毒在仔鼠肠道内的复制及其复制导致的腹泻.采用小干扰RNA(siRNA)敲除发动蛋白2,而非发动蛋白1,可以显著抑制轮状病毒感染,说明dyngo-4a主要通过影响发动蛋白2的功能来抑制轮状病毒.机制层面,dyngo-4a通过作用于发动蛋白2并引起发动蛋白2寡聚体异常积累来发挥其抗轮状病毒感染的功能.由此,dyngo-4a是潜在的特异性靶向治疗轮状病毒腹泻的候选药物.
基金
supported by the National Natural Science Foundation of China(81971976,81772236)to Shuwen Wu
Major Project of Technology Innovation Program of Hubei Province(2018ACA123)to Shuwen Wu and Ke Lan。
