@article {Kim2021.03.15.433877, author = {Dae-Kyum Kim and Benjamin Weller and Chung-Wen Lin and Dayag Sheykhkarimli and Jennifer J. Knapp and Nishka Kishore and Mayra Sauer and Ashyad Rayhan and Veronika Young and Nora Marin-de la Rosa and Oxana Pogoutse and Kerstin Spirohn and Alexandra Strobel and Florent Laval and Patrick Schwehn and Roujia Li and Simin Rothballer and Melina Altmann and Patricia Cassonnet and Guillaume Dugied and Atina G. Cote and Lena Elorduy Vergara and Isaiah Hazelwood and Bingruo B. Liu and Maria Nguyen and Ramakrishnan Pandiarajan and Patricia A. Rodriguez Coloma and Luc Willems and Jean-Claude Twizere and Caroline Demeret and Yves Jacob and Tong Hao and Dave E. Hill and Claudia Falter and Marc Vidal and Michael A. Calderwood and Frederick P. Roth and Pascal Falter-Braun}, title = {A map of binary SARS-CoV-2 protein interactions implicates host immune regulation and ubiquitination}, elocation-id = {2021.03.15.433877}, year = {2021}, doi = {10.1101/2021.03.15.433877}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Key steps in viral propagation, immune suppression, and pathology are mediated by direct, binary, physical interactions between viral and host proteins. To understand the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated an unbiased systematic map of binary interactions between viral and host proteins, complementing previous co-complex association maps by conveying more direct mechanistic understanding and potentially enabling targeted disruption of direct interactions. To this end, we deployed two parallel strategies, identifying 205 virus-host and 27 intraviral binary interactions amongst 171 host and 19 viral proteins, and confirming high quality of these interactions via a calibrated orthogonal assay. Host proteins interacting with SARS-CoV-2 proteins are enriched in various cellular processes, including immune signaling and inflammation, protein ubiquitination, and membrane trafficking. Specific subnetworks provide new hypotheses related to viral modulation of host protein homeostasis and T-cell regulation. The binary virus-host protein interactions we identified can now be prioritized as targets for therapeutic intervention. More generally, we provide a resource of systematic maps describing which SARS-CoV-2 and human proteins interact directly.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/03/18/2021.03.15.433877}, eprint = {https://www.biorxiv.org/content/early/2021/03/18/2021.03.15.433877.full.pdf}, journal = {bioRxiv} }