The IMEx Coronavirus interactome: an evolving map of Coronaviridae-Host molecular interactions

Abstract

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions enables studying fine-grained resolution of the mechanisms behind the virus biology and the human organism response. Here we present a curated dataset of physical molecular interactions, manually extracted by IMEx Consortium curators focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family. Currently, the dataset comprises over 2,200 binarized interactions extracted from 86 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (www.ebi.ac.uk/intact), and will be continuously updated as research on COVID-19 progresses.

The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets

“…SARS-CoV-2 proteins, highlighted in blue, have been added to the standard human protein–protein association network in STRING, using the data add-on (‘payload’) mechanism. Virus proteins will automatically appear in the network based on their known associations with host proteins (as imported from the IMEx coronavirus interactome ( 35 )). In addition, host proteins whose expression appears to control SARS-CoV-2 virion entry into cells, as determined in a recent genome-wide CRISPR-screen ( 36 ), are highlighted: proteins whose removal causes a drop in virus entry efficiency are highlighted in red; green highlights indicate proteins whose removal enhances virus entry.…”

In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm

“…These targets can either be proteins of the virus involved in the mechanisms used to enter the host cell and replicate, or the host proteins that facilitate the spread of the virus or cause over-reactive dangerous responses. Proteomics studies such as the works of Gordon et al [5], Zhou et al [6] or included in databases such as IntAct [7] uncover the target elements of the human interactome. Second, we require to find the treatments that target the key proteins and pathways identified, to either inhibit or activate them in order to undermine the viral load or improve the host response.…”

Comprehensive pathway enrichment analysis workflows: COVID-19 case study

“…All interactions are derived from literature curation in a coordinated effort by multiple databases belonging to the IMEx consortium [ 25 ] . Recently, IntAct introduced an update including interaction data from the high-throughput (HT) multi-level proteomics studies on SARS-CoV-2, SARS and other Coronaviridae [ 26 ]. The IntAct update provides information about molecular interactions extracted from publications concerning viral proteins from the Coronaviridae family and human proteins and other organisms.…”