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CRISPR screens by human betacoronaviruses SARS-CoV-2 and HCoV-OC43 using IGROV-1 cells

ABSTRACT: CRISPR screens by human betacoronaviruses SARS-CoV-2 and HCoV-OC43 using IGROV-1 cells

PROVIDER: PRJNA994011 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25244709.fastq.gz	Fastqsanger.gz
	SRR25244710.fastq.gz	Fastqsanger.gz
	SRR25244711.fastq.gz	Fastqsanger.gz

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CRISPR screens by human betacoronaviruses SARS-CoV-2 and HCoV-OC43 using IGROV-1 cells

Project description:The emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronavirus SARS-CoV-2 and HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, and isolating SARS-CoV-2 variants from patient samples. Using time-course transcriptomics, we confirmed that IGROV-1 cells exhibit a robust innate immune response upon SARS-CoV-2 infection, recapitulating the response previously observed in primary human nasal epithelial cells. We performed genome-wide CRISPR knockout genetic screens in IGROV-1 cells and identified Aryl hydrocarbon receptor (AHR) as a critical host dependency factor for both SARS-CoV-2 and HCoV-OC43. Using DiMNF, a small molecule inhibitor of AHR, we observed that the drug selectively inhibits HCoV-OC43 infection but not SARS-CoV-2. Transcriptomic analysis in primary normal human bronchial epithelial cells revealed that DiMNF blocks HCoV-OC43 infection via basal activation of innate immune responses. Our findings highlight the potential of IGROV-1 cells as a valuable diagnostic and research tool to combat betacoronavirus diseases.

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