Rottlerin plays an antiviral role at early and late steps of Zika virus infection

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 vi...

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Autores principales: Zhou, Shili, Lin, Quanshi, Huang, Changbai, Luo, Xiaotong, Tian, Xu, Liu, Chao, Zhang, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wuhan Institute of Virology, Chinese Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583117/
https://www.ncbi.nlm.nih.gov/pubmed/35934227
http://dx.doi.org/10.1016/j.virs.2022.07.012
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author Zhou, Shili
Lin, Quanshi
Huang, Changbai
Luo, Xiaotong
Tian, Xu
Liu, Chao
Zhang, Ping
author_facet Zhou, Shili
Lin, Quanshi
Huang, Changbai
Luo, Xiaotong
Tian, Xu
Liu, Chao
Zhang, Ping
author_sort Zhou, Shili
collection PubMed
description 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.
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spelling pubmed-95831172022-10-20 Rottlerin plays an antiviral role at early and late steps of Zika virus infection Zhou, Shili Lin, Quanshi Huang, Changbai Luo, Xiaotong Tian, Xu Liu, Chao Zhang, Ping Virol Sin Research Article 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. Wuhan Institute of Virology, Chinese Academy of Sciences 2022-08-05 /pmc/articles/PMC9583117/ /pubmed/35934227 http://dx.doi.org/10.1016/j.virs.2022.07.012 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Zhou, Shili
Lin, Quanshi
Huang, Changbai
Luo, Xiaotong
Tian, Xu
Liu, Chao
Zhang, Ping
Rottlerin plays an antiviral role at early and late steps of Zika virus infection
title Rottlerin plays an antiviral role at early and late steps of Zika virus infection
title_full Rottlerin plays an antiviral role at early and late steps of Zika virus infection
title_fullStr Rottlerin plays an antiviral role at early and late steps of Zika virus infection
title_full_unstemmed Rottlerin plays an antiviral role at early and late steps of Zika virus infection
title_short Rottlerin plays an antiviral role at early and late steps of Zika virus infection
title_sort rottlerin plays an antiviral role at early and late steps of zika virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9583117/
https://www.ncbi.nlm.nih.gov/pubmed/35934227
http://dx.doi.org/10.1016/j.virs.2022.07.012
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