Covid-19 protein-protein interaction mapping – Cov2PIM

The identification of virus-virus and virus-host protein-protein interactions is a determinant element for the understanding of the mechanisms of replication and viral transmission. The knowledge of the molecular details of these protein interactions is a prerequisite for the discovery of new therapeutic targets to address and fight viral diseases. Several articles have recently demonstrated the mechanisms of the entry of the virus into the host via the angiotensin converting enzyme II (ACE2) receptor but little is known about the other potential interactions between viral proteins and the host.
In the context of the global battle against SARS-CoV-2, we propose a research program that aims to establish a comprehensive map of interactions between viral and host proteins but also between the viral proteins themselves.
Hybrigenics Services is the word leader in the domain of protein-protein interactions, thanks to its proprietary Yeast Two-Hybrid technology. We have already led many project studying viral-host protein-protein interactions including studies on the SARS-CoV virus. Our previous experience on SARS-CoV will be helpful to design the optimal regions of the SARS-CoV-2 proteins to be used for the Y2H screens. Thanks to our 20 years of experience we already know the highly connected proteins and technical false positives of the technique. The fact that an operational yeast two-hybrid (Y2H)- platform as well as sophisticated bioinformatics analysis tools for the identification of novel protein interactions are already available at Hybrigenics Services is a key factor for the success of the project and the rapid free access for the research community to the results of the virus-host and the virus-virus interaction map in four to ten months.
We already took part in research program where we have deposited several large-scale protein interaction data in the INTACT database. Similarly, the SARS-CoV-2 protein interaction maps will be made available to the research community in INTACT and the PPI network will be displayed using open source software like Cytoscape. Knowing the protein-protein interaction that occur between the viral proteins and between the virus and the host will allow to better understand the intra-cellular mechanisms used to escape the host defense and open up new ways for the identification of novel targets for therapy.
As an example, some publications have shown that disruption on viral protein interaction of the SARS-CoV nsp10/nsp14 are lethal. Therefore, such virus-virus protein interactions constitute interesting new targets for the development of antiviral compounds. Similar strategy has been employed for the HIV and compounds that disrupt the integrase/LEDGF interaction are currently in clinical trial.
Finally, our direct contact with teams implicated in viral protein interaction inhibition (virus/virus or virus host) and coronavirus research (X. Morelli CRCM/CNRS Marseilles, J-C Guillemot and E. Decroly in the Bruno Canard Laboratory AFMB UMR 7257) will assure the proper and rapid usage of the open data provided by Hybrigenics Services.