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Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy
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research paper
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Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy
Creator
Wang, Lin-Fa
Niu, Peihua
Tan, Wenjie
Huang, Baoying
Ye, Fei
Cui, Jin
Sigmundsson, Kristmundur
Anderson, Danielle
Kim, So
Gong, Jing
Lim, Xiao
Liu, Weiqiang
Tan, Xu
Yan, Biao
Ye, Qian
Zhou, Xuming
Zu, Wenhong
Source
BioRxiv
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 broad spectrum antiviral therapy.
has issue date
2020-03-30
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bibo:doi
10.1101/2020.03.29.014209
has license
biorxiv
sha1sum (hex)
681abe795769a807b043603ae723815aa57b00eb
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https://doi.org/10.1101/2020.03.29.014209
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Orthogonal genome-wide screenings in bat cells identify MTHFD1 as a target of broad antiviral therapy
schema:publication
bioRxiv
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covid:681abe795769a807b043603ae723815aa57b00eb#body_text
is
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named entity 'MERS-CoV'
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named entity 'Middle East Respiratory Syndrome'
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named entity 'virus'
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