A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Purposing

ABSTRACT: An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 170,000 people since the end of 2019, killed over 7,400, and caused worldwide social and economic disruption. SARS-CoV-2 infection has a mortality rate of 3.4% among confirmed cases, and there are currently no effective antiviral molecules or vaccines for its treatment or prevention. The search for effective antiviral treatments has recently highlighted host-directed strategies, however besides data describing viral interactions with cell surface receptors and activating proteases, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To shed light on the mechanisms used by SARS-CoV-2 to infect human cells, we have utilized affinity-purification mass spectrometry to globally profile physical host protein interactions for 26 viral proteins encoded in the SARS-CoV-2 genome, identifying 332 high confidence interactions. Among the human proteins, we identify many druggable human proteins targeted by existing FDA approved drugs that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host-dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral targets against SARS-CoV-2 and other deadly coronavirus strains.

INSTRUMENT(S): Exactive Plus

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Danielle Swaney  

LAB HEAD: Nevan Krogan

PROVIDER: PXD018117 | Pride | 2020-03-23

REPOSITORIES: Pride