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

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 disruption 1,2 . 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.

Structural insight into the putative role of novel SARS CoV-2 E protein in viral infection: a potential target for LAV development and therapeutic strategies

“…While there are no antiviral drugs or effective vaccines against COVID-19 on the market; we leverage the existing knowledge of viral channel proteins and structural modeling to explain a putative mechanism involving E protein in SARS-CoV-2 related infection. The development of therapeutic approaches is being hindered due to the lack of understanding of molecular mechanisms and molecular players responsible for this novel viral infection (5). The possibility of E protein being a vaccine candidate has already been explored with the MERS-CoV; certain mutations towards the C-terminal end combined with mutations in the NS1 protein resulted in a stable vaccine against the virus, overcoming the pathogenesis of the revertant mutants (16).…”

A Role for Metal-Based Drugs in Fighting COVID-19 Infection? The Case of Auranofin

“…Despite the intense research efforts, we were surprised in learning that no metal compound is currently being tested against the SARS-CoV-2 virus. 1 Metal based agents form a variegate and attractive class of drugs with a number of therapeutic applications: we strongly encourage the international scientific community to fill this gap quickly and explore the potential of metallodrugs against COVID-19 disease.…”

Lung Disease Network Reveals the Impact of Comorbidity on SARS-CoV-2 infection

“…To depict the SARS-CoV-2 -host interaction network, the protein-protein interactions (PPI) network of lungs was obtained from the TissueNet v.2 database [10]. We collected the list of 332 human targets of SARS-CoV-2 from Gordon et al [8] article and constructed the subnetwork of these 332 proteins from the PPI network of lungs. Out of the 332 viral targets, 323 proteins were present in the subnetwork.…”

“…We downloaded 168296 lung-specific interactions from TissueNet v.2 to construct SARS-CoV-2 targets interactome. Next, we obtained the list of 332 human proteins targeted by SARS-CoV-2 [8] and built a subnetwork, called the SARS-CoV-2 target network (STN). The 9…”