New research published by the University of California has revealed over 230 interactions that COVID-19 proteins establish with human proteins. This work offers insights into how COVID-19 infection occurs and identifies almost 70 potential drug-targets.
Coronavirus Disease-2019 (COVID-19) has infected over 1,030,000 people in more than 100 countries (data 03/04/2020), but due to a lack of known molecular detail, there are no current antiviral compounds available to combat the virus. Interactions between host cell proteins and viral proteins are at the forefront of infection, where viruses such as COVID-19 hijack host resources to propagate. There is an ever-developing arms race between host antiviral factors, which aim to hinder infection, and viral antagonistic factors, which aim to counteract host defences. Revealing this complex network of interactions can help us understand how viral infection occurs and can reveal therapeutic targets to combat infection.
The Krogan labrevealed the interactions of 26 of the 29 COVID-19 proteins in human cells using a technique known as affinity purification followed by mass spectroscopy (AP-MS, Figure A), which allowed them to probe protein-protein complexes with high sensitivity. The researchers identified over 230 human interactors which participate in a wide array of key cellular pathways such as innate immunity and the protein unfolded response (Figure B). Using bioinformatic analysis, they reveal almost 70 compounds which target key parts of the network and may represent potential antiviral drugs. Current tests for antiviral activity are ongoing. The work also reveals many common interaction partners between COVID-19 and other viruses also associated with pulmonary conditions such as West Nile Virus and Mycobacterium tuberculosis, suggesting that they may have similar mechanisms of infection.
This work contributes significantly to our current understanding of COVID-19 and furthers our efforts to find compounds which may combat infection.
Written by Catherine Truman, DTP DPhil student
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing. David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Matthew J. O’Meara, […], Pedro Beltrao, Kevan Shokat, Brian K. Shoichet, Nevan J. Krogan,. BioRxiv. DOI: https://doi.org/10.1101/2020.03.22.002386