Abstract
AbstractSeveral molecular datasets have been recently compiled to characterize the activity of SARS-CoV-2 within human cells. Here we extend computational methods to integrate several different types of sequence, functional and interaction data to reconstruct networks and pathways activated by the virus in host cells. We identify key proteins in these networks and further intersect them with genes differentially expressed at conditions that are known to impact viral activity. Several of the top ranked genes do not directly interact with virus proteins. We experimentally tested treatments for a number of the predicted targets. We show that blocking one of the predicted indirect targets significantly reduces viral loads in stem cell-derived alveolar epithelial type II cells (iAT2s).Software and interactive visualizationhttps://github.com/phoenixding/sdremsc
Publisher
Cold Spring Harbor Laboratory
Reference55 articles.
1. M. Hoffmann , H. Kleine-Weber , S. Schroeder , N. Krüger , T. Herrler , S. Erichsen , T. S. Schiergens , G. Herrler , N.-H. Wu , A. Nitsche , et al., “SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor,” Cell, 2020.
2. Y. Fu , Y. Cheng , and Y. Wu , “Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools,” Virol Sin, pp. 1–6, 2020.
3. D. E. Gordon , G. M. Jang , M. Bouhaddou , J. Xu , et al., “A SARS-CoV-2 protein interaction map reveals targets for drug repurposing,” Nature, pp. 1–44, 2020.
4. A. Stukalov , V. Girault , V. Grass , V. Bergant , et al., “Multilevel proteomics reveals host perturbations by sars-cov-2 and sars-cov,” Nature, 2021.
5. Genetic diversity and evolution of SARS-CoV-2;Infec Genet Evol,2020