{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:51:58Z","timestamp":1788367918997,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017-05631"],"award-info":[{"award-number":["2017-05631"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2015-00162"],"award-info":[{"award-number":["2015-00162"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2017-03407"],"award-info":[{"award-number":["2017-03407"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC-2016-PoC 755150"],"award-info":[{"award-number":["ERC-2016-PoC 755150"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Swiss National Foundation Fellowship","award":["P2ZHP3_158770"],"award-info":[{"award-number":["P2ZHP3_158770"]}]},{"name":"EMBO Long-Term Fellowship","award":["ALTF-1140-2015"],"award-info":[{"award-number":["ALTF-1140-2015"]}]},{"DOI":"10.13039\/501100001729","name":"Stiftelsen f\u00f6r Strategisk Forskning","doi-asserted-by":"publisher","award":["FID15-0010"],"award-info":[{"award-number":["FID15-0010"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001729","name":"Stiftelsen f\u00f6r Strategisk Forskning","doi-asserted-by":"publisher","award":["IB13-0074"],"award-info":[{"award-number":["IB13-0074"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020","award":["722729"],"award-info":[{"award-number":["722729"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>RNA viruses have gained plenty of attention during recent outbreaks of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and Ebola virus. ZIKV is a vector borne Flavivirus that is spread by mosquitoes and it mainly infects neuronal progenitor cells. One hallmark of congenital ZIKV disease is a reduced brain size in fetuses, leading to severe neurological defects. The World Health Organization (WHO) is urging the development of new antiviral treatments against ZIKV, as there are no efficient countermeasures against ZIKV disease. Previously, we presented a new class of host-targeting antivirals active against a number of pathogenic RNA viruses, such as SARS-CoV-2. Here, we show the transfer of the image-based phenotypic antiviral assay to ZIKV-infected brain cells, followed by mechanism-of-action studies and a proof-of-concept study in a three-dimensional (3D) organoid model. The novel antiviral compounds showed a therapeutic window against ZIKV in several cell models and rescued ZIKV-induced neurotoxicity in brain organoids. The compound\u2019s mechanism-of-action was pinpointed to late steps in the virus life cycle, impairing the formation of new virus particles. Collectively, in this study, we expand the antiviral activity of new small molecule inhibitors to a new virus class of Flaviviruses, but also uncover compounds\u2019 mechanism of action, which are important for the further development of antivirals.<\/jats:p>","DOI":"10.3390\/v13010037","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T19:55:25Z","timestamp":1609271725000},"page":"37","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Broadly Active Antiviral Compounds Disturb Zika Virus Progeny Release Rescuing Virus-Induced Toxicity in Brain Organoids"],"prefix":"10.3390","volume":"13","author":[{"given":"Aleksandra","family":"Pettke","sequence":"first","affiliation":[{"name":"Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5744-3206","authenticated-orcid":false,"given":"Marianna","family":"Tampere","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Stockholm, Sweden"},{"name":"National Veterinary Institute, 756 51 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1831-588X","authenticated-orcid":false,"given":"Robin","family":"Pronk","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6481-237X","authenticated-orcid":false,"given":"Olov","family":"Wallner","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-8610","authenticated-orcid":false,"given":"Anna","family":"Falk","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"Warpman Berglund","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Helleday","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Mirazimi","sequence":"additional","affiliation":[{"name":"National Veterinary Institute, 756 51 Uppsala, Sweden"},{"name":"Unit of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute and Karolinska University Hospital, 171 77 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9936-9734","authenticated-orcid":false,"given":"Marjo-Riitta","family":"Puumalainen","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 171 65 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020, November 26). 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