Genome-scale CRISPR screens identify host factors that promote human coronavirus infection

• DOI: 10.1186/s13073-022-01013-1
• Publication Date: 2022-01-27T10:02:55Z
• Authors: Marco Grodzki; Andrew P. Bluhm; Moritz Schaefer; Abderrahmane Tagm...; Max Russo; Amin Sobh; Roya Rafiee; Chris D. Vulpe; Stephanie M. Karst; Michael H. Norris
• Keywords: Coronavirus; Vero cell; Viral life cycle; HEK 293 cells

Abstract Background The COVID-19 pandemic has resulted in 275 million infections and 5.4 deaths as of December 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies antigenically novel SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step their life cycle, representing rich pool candidate targets drug design. Methods To identify that promote infection with potential broad-spectrum activity coronavirus family, we performed genome-scale CRISPR knockout screens two cell lines (Vero E6 HEK293T ectopically expressing ACE2) common cold-causing human OC43. Gene knockdown, knockout, small molecule testing Vero, HEK293, airway epithelial cells were used verify our findings. Results identified multiple genes functional pathways have been previously reported replication, also substantial number pathways. website https://sarscrisprscreens.epi.ufl.edu/ was created allow visualization comparison SARS-CoV2 uniformly analyzed way. Of note, involved cycle regulation enriched several key components programmed mRNA decay pathway. role EDC4 XRN1 replication verified. Finally, compounds targeting revealed by screens. Conclusions Overall, studies substantiate expand growing body literature focused on understanding coronavirus-host interactions exploit knowledge rational development.