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 envel...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 PKCδor 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.展开更多
基金supported by Guangzhou Municipal Science and Technology Program (202206010114)National Natural Science Foundation of China (31970887, 92169110)+1 种基金Doctoral workstation foundation of Guangdong Second Provincial General hospital (2020BSGZ036)Natural Science Foundation of Guangdong Province(2021A1515011491, 2022A1515010451)
文摘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 PKCδor 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.
