Determination of host cell proteins constituting the molecular microenvironment of coronavirus replicase complexes by proximity-labeling

V’kovski Philip; Gerber Markus; Kelly Jenna; Pfaender Stephanie; Ebert Nadine; Braga Lagache Sophie; Simillion Cedric; Portmann Jasmine; Stalder Hanspeter; Gaschen Véronique; Bruggmann Remy; Stoffel Michael; Heller Manfred; Dijkman Ronald; Thiel Volker

One novel finding that arose immediately from our RTC-proximity screen is the demonstration 385 of a close spatial association of host cell translation with the coronavirus RTC. Indeed, the 386 biotin ligase-based proteomic screen identified a number of translation initiation factors, most 387 prominently several eIF3 subunits that were found to have functional importance for viral 388 replication, and numerous ribosome-and translation-associated proteins within the coronavirus 389 RTC microenvironment (Fig. 3, 4) . In addition, the presence of subunits of the signal uncorrected Dunn's test) was used to test the statistical significance of reduced viral replication 641 (mean < 95% as compared to scramble control, n=216). The R package ggplot2 was used to 642 create the bubble plot (Fig 4B) . The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/417907 doi: bioRxiv preprint