A Comprehensive Human cDNA Library For Functional Gene Replacement in Drosophila

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PROJECT SUMMARY The recent pandemic of COVID-19 due to infection with the SARS-CoV-2 coronavirus has created an urgent need to understand the biological mechanisms of pathogenesis of this new disease. The SARS-CoV-2 is a coronavirus with a slightly less than 30 kilobases (kb) long RNA genome that encodes 26 proteins that interact with several hundred human proteins and initiate a number of pathogenic steps. Here we use the genetic model Drosophila melanogaster to understand gene and protein function involved in COVID-19. We will generate a library of UAS-cDNA constructs and transgenic flies to express and functionally assess the viral proteins. We will also generate transgenic flies for over 300 genes in the human genome involved in viral replication and COVID-19 disease. We will generate Drosophila reagents for the Drosophila homologs of these human genes using a unique drop-in technology and we will update the online hub for the dissemination of these resources to Drosophila labs throughout the world.