Identifying potential drug targets for fighting SARS-CoV-2
The novel SARS-CoV-2 coronavirus has infected more than 2.5 million people globally and is still rapidly spreading. Unfortunately, an antiviral drug or vaccine has not yet been developed. Scientists require a clear understanding of how the virus hijacks the host cells upon infection; information that is crucial to developing therapies to combat this virus.
In a study that has been available on Biorxiv since the last month, researchers from the USA, UK and France have detected the human proteins that physically interact with the SARS-CoV-2 virus. This paper has also identified, among these, the human proteins that are already targets for existing drugs or compounds that are currently being tested as antiviral drugs.
To identify the human proteins that interact with SARS-CoV-2, the researchers used affinity purification, a process that identifies physical interactors based on the ability of proteins to bind to each other on a matrix. The bound interactors were then identified through mass spectrometry.
The researchers found that the SARS-CoV-2 virus interacts with multiple proteins involved in processes such as immune system activation, host membrane fusion and protein degradation, among others. Certain viral proteins also bind to specific regions in the host DNA and alter the host protein production to its own benefit.
Once the physical interactors were identified, the researchers used a chemoinformatics approach to identify potential drugs and compounds that target these interactors. The potential antiviral will bind to the human protein and prevent the virus from binding to it. This decreases the chance of further infection.
The scientists have identified 66 drugs and small molecules, some of which have made headlines recently. The drug chloroquine targets some of the human proteins which interact with the virus, making it a candidate for further studies. However, the researchers do not claim to have identified a mechanism of this interaction yet and trials are still ongoing.
Antibiotics like bafilomycin A1, azithromycin, chloramphenicol, tigecycline, and linezolid; the anticonvulsant valproic acid; and the antipsychotic haloperidol also target proteins that interact with the virus. These drugs therefore merit further studies and many of them are already in clinical trials.
Understanding the interaction between human and viral proteins is crucial to developing an antiviral therapy. This study has helped identify targets for repurposing already existing drugs as well as identified novel protein targets, paving the way for scientists to develop a therapy to fight SARS-CoV-2 in the future
Aditi Karmarkar is an alumnus of the Tata Institute of Fundamental Research, Mumbai. She currently works as a medical writer for a pharmaceutical company and freelances as a science writer in her spare time.