A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

Nature
David E GordonNevan J Krogan

Abstract

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharma...Continue Reading

Associated Clinical Trials

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Methods Mentioned

BETA
affinity purification
X-ray
ubiquitination
neddylation
PCR
Transfection

Clinical Trials Mentioned

NCT04332991

Software Mentioned

Reactome
IDT
REDO
IntAct
MaxQuant
CORUM
pyrosetta
R
SAINTexpress
QCloud

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