Title: Shared host genetic landscape of respiratory viral infection

Authors: Leah Soriaga, Dale Balce, Istvan Bartha, Arnold Park, Emily Wong, Michael McAllaster, Elizabeth A. Mueller, Ona Barauskas, Esteban Carabajal, Beatriz Kowalski, Sooyoung Lee, Gary Lo, Tara F. ‘Penny’ Mahoney, Matteo Metruccio, Anna Sahakyan, Logeshwaran Somasundaram, Tod Steinfeld, Lisha Wang, Laura Wedel, Samantha S. Yim, Li Yin, Jiayi Zhou, Zach Newby, Winston Tse, Johannes Grosse, Herbert Skip Virgin, Seungmin Hwang, Amalio Telenti

Abstract: Respiratory viruses represent a major global health burden. Although these viruses have different life cycles, they may depend on common host genetic factors, which could be targeted by broad-spectrum host-directed therapies. We used genome-wide CRISPR screens and advanced data analytics to map a network of host genes that support infection by nine human respiratory viruses (influenza A virus, parainfluenza virus, human rhinovirus, respiratory syncytial virus, human coronavirus (HCoV)-229E, HCoV-NL63, HCoV-OC43, MERS-CoV, and SARS-CoV-2). We found shared pathways that we explored, using knowledge graphs to inform on pharmacological targets. We selected and validated STT3A/B proteins of the N-oligosaccharyltransferase complex as host targets of broad-spectrum antiviral small molecules. Our work highlights the commonalities of viral host genetic dependencies and the feasibility of using this information to develop broad-spectrum antiviral agents.

Downloads:

• Files_S1_Genomewide_CRISPR_MAGeCK_Gene_Summary.zip - Zip file of all screens.