Publication Date
8-29-2023
Journal
Cell Reports
DOI
10.1016/j.celrep.2023.112842
PMID
37480566
PMCID
PMC10962759
PubMedCentral® Posted Date
3-25-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Humans, Animals, SARS-CoV-2, COVID-19, Drosophila, Actins, Animals, Genetically Modified
Abstract
Development of effective therapies against SARS-CoV-2 infections relies on mechanistic knowledge of virus-host interface. Abundant physical interactions between viral and host proteins have been identified, but few have been functionally characterized. Harnessing the power of fly genetics, we develop a comprehensive Drosophila COVID-19 resource (DCR) consisting of publicly available strains for conditional tissue-specific expression of all SARS-CoV-2 encoded proteins, UAS-human cDNA transgenic lines encoding established host-viral interacting factors, and GAL4 insertion lines disrupting fly homologs of SARS-CoV-2 human interacting proteins. We demonstrate the utility of the DCR to functionally assess SARS-CoV-2 genes and candidate human binding partners. We show that NSP8 engages in strong genetic interactions with several human candidates, most prominently with the ATE1 arginyltransferase to induce actin arginylation and cytoskeletal disorganization, and that two ATE1 inhibitors can reverse NSP8 phenotypes. The DCR enables parallel global-scale functional analysis of SARS-CoV-2 components in a prime genetic model system.
Graphical Abstract
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Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Clinical Epidemiology Commons, COVID-19 Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons