Forced association of SARS-CoV-2 proteins with the yeast proteome perturb vesicle trafficking

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the highly infectious coronavirus disease COVID-19. Extensive research has been performed in recent months to better understand how SARS-CoV-2 infects and ma-nipulates its host to identify potential drug targets and support patient recovery from COVID-19. However, the function of many SARS-CoV-2 proteins remains uncharacterised. Here we used the Synthetic Physical Interactions (SPI) method to recruit SARS-CoV-2 proteins to most of the budding yeast proteome to identify conserved pathways which are affected by SARS-CoV-2 proteins. The set of yeast proteins that result in growth defects when asso-ciated with the viral proteins have homologous functions that overlap those identified in studies performed in mammalian cells. Specifically, we were able to show that recruiting the SARS-CoV-2 NSP1 protein to HOPS, a vesicle-docking complex, is sufficient to perturb membrane trafficking in yeast consistent with the hijack-ing of the endoplasmic-reticulum–Golgi intermediate compart-ment trafficking pathway during viral infection of mammalian cells. These data demonstrate that the yeast SPI method is a rap-id way to identify potential functions of ectopic viral proteins.

Keywords

• sars-cov-2
• covid-19
• synthetic physical interactions
• vesicle trafficking
• transcription