{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["McNulty J"],"funding":["Natural Sciences and Engineering Research Council of Canada","National Institute of Neurological Disorders and Stroke","NEI NIH HHS","Research to Prevent Blindness","NINDS NIH HHS","Stanley Medical Research In"],"pagination":["1639"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9885069"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["The total synthesis of four novel mono-methoxy and hydroxyl substituted ring-A dihydronarciclasine derivatives enabled identification of the 7-hydroxyl derivative as a potent and selective antiviral agent targeting SARSCoV-2 and HSV-1. The concentration of this small molecule that inhibited HSV-1 infection by 50% (IC50), determined by using induced pluripotent stem cells (iPCS)-derived brain organ organoids generated from two iPCS lines, was estimated to be 0.504 µM and 0.209 µM. No significant reduction in organoid viability was observed at concentrations up to 50 mM. Genomic expression analyses revealed a significant effect on host-cell innate immunity, revealing activation of the integrated stress response via PERK kinase upregulation, phosphorylation of eukaryotic initiation factor 2α "],"journal":["Scientific reports"],"pubmed_title":["Truncated ring-A amaryllidaceae alkaloid modulates the host cell integrated stress response, exhibiting antiviral activity to HSV-1 and SARSCoV-2."],"pmcid":["PMC9885069"],"funding_grant_id":["1R01NS115082-01A1","R21 NS096405","13R-002","P30 EY008098","EY08098","R01 NS115082"],"pubmed_authors":["Nimgaonkar VL","McNulty J","Scattolon J","Babu-Dokuburra C","Kinchington PR","D'Aiuto L","Caldwell JK","Wesesky MA","Milosevic J","Bloom DC","Zheng W","Zepeda-Velazquez C"],"additional_accession":[]},"is_claimable":false,"name":"Truncated ring-A amaryllidaceae alkaloid modulates the host cell integrated stress response, exhibiting antiviral activity to HSV-1 and SARSCoV-2.","description":"The total synthesis of four novel mono-methoxy and hydroxyl substituted ring-A dihydronarciclasine derivatives enabled identification of the 7-hydroxyl derivative as a potent and selective antiviral agent targeting SARSCoV-2 and HSV-1. The concentration of this small molecule that inhibited HSV-1 infection by 50% (IC50), determined by using induced pluripotent stem cells (iPCS)-derived brain organ organoids generated from two iPCS lines, was estimated to be 0.504 µM and 0.209 µM. No significant reduction in organoid viability was observed at concentrations up to 50 mM. Genomic expression analyses revealed a significant effect on host-cell innate immunity, revealing activation of the integrated stress response via PERK kinase upregulation, phosphorylation of eukaryotic initiation factor 2α ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-07-14T20:06:01.842Z","creation":"2024-11-19T19:16:09.044Z"},"accession":"S-EPMC9885069","cross_references":{"pubmed":["36717567"],"doi":["10.1038/s41598-023-28691-0"]}}