Mar 30, 2020

Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy

BioRxiv : the Preprint Server for Biology
D. E. Anderson

Abstract

Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing b...Continue Reading

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Mentioned in this Paper

Study
Methylene dimethanesulfonate
Untranslated Regions
Pluripotent Stem Cells
Genome
Genes
Regulation of Biological Process
Sequence Determinations, RNA
Transcription, Genetic
Human Induced Pluripotent Stem Cells

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