Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China; Medical Research Center, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China.
Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, China; Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Virol Sin. 2022 Oct;37(5):685-694. doi: 10.1016/j.virs.2022.07.012. Epub 2022 Aug 5.
Infection of Zika virus (ZIKV) may cause microcephaly and other neurological disorders, while no vaccines and drugs are available. Our study revealed that rottlerin confers a broad antiviral activity against several enveloped viruses, including ZIKV, vesicular stomatitis virus, and herpes simplex virus, but not against two naked viruses (enterovirus 71 and encephalomyocarditis virus). Rottlerin does not have a direct virucidal effect on the virions, and its antiviral effect is independent of its regulation on PKCδ or ATP. Both pretreatment and post-treatment of rottlerin effectively reduce the viral replication of ZIKV. The pretreatment of rottlerin disturbs the endocytosis of enveloped viruses, while the post-treatment of rottlerin acts at a late stage through disturbing the maturation of ZIKV. Importantly, administration of rottlerin in neonatal mice significantly decreased the ZIKV replication in vivo, and alleviated the neurological symptoms caused by ZIKV. Our work suggests that rottlerin exerts an antiviral activity at two distinct steps of viral infection, and can be potentially developed as a prophylactic and therapeutic agent.
寨卡病毒（ZIKV）感染可能导致小头畸形和其他神经紊乱，而目前尚无疫苗和药物可用。我们的研究表明，罗特林菌素对几种包膜病毒具有广泛的抗病毒活性，包括寨卡病毒、水疱性口炎病毒和单纯疱疹病毒，但对两种裸露病毒（肠道病毒 71 和脑炎心肌炎病毒）没有作用。罗特林菌素对病毒粒子没有直接的杀病毒作用，其抗病毒作用与其对 PKCδ或 ATP 的调节无关。罗特林菌素的预处理和后处理均可有效抑制寨卡病毒的复制。罗特林菌素的预处理会干扰包膜病毒的内吞作用，而罗特林菌素的后处理则通过干扰寨卡病毒的成熟作用于晚期阶段。重要的是，罗特林菌素在新生小鼠中的给药显著降低了体内的寨卡病毒复制，并减轻了寨卡病毒引起的神经症状。我们的工作表明，罗特林菌素在病毒感染的两个不同阶段发挥抗病毒活性，可作为预防和治疗药物进行开发。
