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

Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Huettenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZC, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I,

10.1038/s41586-020-2286-9

Research curated

Abstract

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

Source: PubMed

Related molecules

Name	Synonyms	Genes
zotatifin
ternatin-4
PD-144418
Sigma-1 receptor	SIGMAR1, ALS16, OPRS1, SIG-1R, SR-BP, SR-BP1, SRBP, hSigmaR1, sigma1R, DSMA2, sigma non-opioid intracellular receptor 1
clemastine
Cloperastine
progesterone
siramesine
Unspecific
Haloperidol
Hydroxychloroquine	HCQ, Oxichlorochine, Oxichloroquine

Related interactions

Target	Drug	Type	Result
Unspecific	zotatifin	In vitro	positive
Unspecific	ternatin-4	In vitro	positive
Sigma-1 receptor	Haloperidol	In vitro	positive
Sigma-1 receptor	PD-144418	In vitro	positive
Sigma-1 receptor	clemastine	In vitro	positive
Sigma-1 receptor	Cloperastine	In vitro	positive
Sigma-1 receptor	progesterone	In vitro	positive
Unspecific	siramesine	In vitro	positive
Unspecific	Hydroxychloroquine	In vitro	positive