A proteome-scale map of the SARS-CoV-2-human contactome.

Understanding the mechanisms of coronavirus disease 2019 (COVID-19) disease severity to efficiently design therapies for emerging virus variants remains an urgent challenge of the ongoing pandemic. Infection and immune reactions are mediated by direct contacts between viral molecules and the host proteome, and the vast majority of these virus-host contacts (the 'contactome') have not been identified. Here, we present a systematic contactome map of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with the human host encompassing more than 200 binary virus-host and intraviral protein-protein interactions. We find that host proteins genetically associated with comorbidities of severe illness and long COVID are enriched in SARS-CoV-2 targeted network communities. Evaluating contactome-derived hypotheses, we demonstrate that viral NSP14 activates nuclear factor κB (NF-κB)-dependent transcription, even in the presence of cytokine signaling. Moreover, for several tested host proteins, genetic knock-down substantially reduces viral replication. Additionally, we show for USP25 that this effect is phenocopied by the small-molecule inhibitor AZ1. Our results connect viral proteins to human genetic architecture for COVID-19 severity and offer potential therapeutic targets.

Novel Pseudomonas sp. SCA7 Promotes Plant Growth in Two Plant Families and Induces Systemic Resistance in Arabidopsis thaliana.

Pseudomonas sp. SCA7, characterized in this study, was isolated from roots of the bread wheat Triticum aestivum. Sequencing and annotation of the complete SCA7 genome revealed that it represents a potential new Pseudomonas sp. with a remarkable repertoire of plant beneficial functions. In vitro and in planta experiments with the reference dicot plant A. thaliana and the original monocot host T. aestivum were conducted to identify the functional properties of SCA7. The isolate was able to colonize roots, modify root architecture, and promote growth in A. thaliana. Moreover, the isolate increased plant fresh weight in T. aestivum under unchallenged conditions. Gene expression analysis of SCA7-inoculated A. thaliana indicated a role of SCA7 in nutrient uptake and priming of plants. Moreover, confrontational assays of SCA7 with fungal and bacterial plant pathogens revealed growth restriction of the pathogens by SCA7 in direct as well as indirect contact. The latter indicated involvement of microbial volatile organic compounds (mVOCs) in this interaction. Gas chromatography-mass spectrometry (GC-MS) analyses revealed 1-undecene as the major mVOC, and octanal and 1,4-undecadiene as minor abundant compounds in the emission pattern of SCA7. Additionally, SCA7 enhanced resistance of A. thaliana against infection with the plant pathogen Pseudomonas syringae pv. tomato DC3000. In line with these results, SA- and JA/ET-related gene expression in A. thaliana during infection with Pst DC3000 was upregulated upon treatment with SCA7, indicating the ability of SCA7 to induce systemic resistance. The thorough characterization of the novel Pseudomonas sp. SCA7 showed a remarkable genomic and functional potential of plant beneficial traits, rendering it a promising candidate for application as a biocontrol or a biostimulation agent.