Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.antiviral.2023.105732
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dc.titleChelerythrine chloride inhibits Zika virus infection by targeting the viral NS4B protein
dc.contributor.authorLoe, Marcus Wing Choy
dc.contributor.authorLee, Regina Ching Hua
dc.contributor.authorChin, Wei-Xin
dc.contributor.authorMin, Nyo
dc.contributor.authorTeo, Zi Yun
dc.contributor.authorHo, Si Xian
dc.contributor.authorYi, Bowen
dc.contributor.authorChu, Justin Jang Hann
dc.date.accessioned2024-01-29T11:28:42Z
dc.date.available2024-01-29T11:28:42Z
dc.date.issued2023-11
dc.identifier.citationLoe, Marcus Wing Choy, Lee, Regina Ching Hua, Chin, Wei-Xin, Min, Nyo, Teo, Zi Yun, Ho, Si Xian, Yi, Bowen, Chu, Justin Jang Hann (2023-11). Chelerythrine chloride inhibits Zika virus infection by targeting the viral NS4B protein. ANTIVIRAL RESEARCH 219. ScholarBank@NUS Repository. https://doi.org/10.1016/j.antiviral.2023.105732
dc.identifier.issn0166-3542
dc.identifier.issn1872-9096
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/246881
dc.description.abstractZika virus (ZIKV) is a mosquito-borne virus that has re-emerged as a significant threat to global health in the recent decade. Whilst infections are primarily asymptomatic, the virus has been associated with the manifestation of severe neurological complications. At present, there is still a lack of approved antivirals for ZIKV infections. In this study, chelerythrine chloride, a benzophenanthridine alkaloid, was identified from a mid-throughput screen conducted on a 502-compound natural products library to be a novel and potent inhibitor of ZIKV infection in both in-vitro and in-vivo assays. Subsequent downstream studies demonstrated that the compound inhibits a post-entry step of the viral replication cycle and is capable of disrupting viral RNA synthesis and protein expression. The successful generation and sequencing of a ZIKV resistant mutant revealed that a single S61T mutation on the viral NS4B allowed ZIKV to overcome chelerythrine chloride inhibition. Further investigation revealed that chelerythrine chloride could directly inhibit ZIKV protein synthesis, and that the NS4B–S61T mutation confers resistance to this inhibition. This study has established chelerythrine chloride as a potential candidate for further development as a therapeutic agent against ZIKV infection.
dc.language.isoen
dc.publisherELSEVIER
dc.sourceElements
dc.subjectZika
dc.subjectAntiviral
dc.subjectNatural compounds
dc.subjectScreening
dc.subjectNNS4B protein
dc.typeArticle
dc.date.updated2024-01-29T03:07:06Z
dc.contributor.departmentMICROBIOLOGY AND IMMUNOLOGY
dc.description.doi10.1016/j.antiviral.2023.105732
dc.description.sourcetitleANTIVIRAL RESEARCH
dc.description.volume219
dc.published.statePublished
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