Comprehensive protein interaction network helps researchers discover drug candidates for the treatment of COVID-19

Treatment options for COVID-19 are still limited

Understanding the pathogenesis of the virus at the molecular level is the key to developing effective therapies for COVID-19

SARS-CoV-2 infection will significantly change the environment in the host cell, making it possible for the virus to replicate and spread

"In order to effectively find drugs that can change virus replication, we need to know which human proteins and viral proteins interact and how they interact

Reuse existing drug molecules faster

Researchers from the University of Helsinki (Institute of Biotechnology, Finnish Institute of Molecular Medicine) and the University of Eastern Finland have used modern technology, proteomics and chemoinformatics combined with high-throughput screening in the drug discovery process to solve this task

In order to effectively search for drugs that can alter virus replication, they first comprehensively mapped the physical, functional, and transient interactions between viral proteins and human host cells

The analysis identified hundreds of host proteins used for virus replication, and then used them as a reasonable resource for drug reuse through virtual screening methods

Varjosalo said: "The repurposing of existing drug molecules is much faster than traditional strategies, rather than investing in new drugs, because their applicability and safety have been established

The study recommends 59 compounds for 15 protein targets

The entire process led to the proposed reuse of 59 compounds for 15 protein targets

In addition, 6 candidate drugs have proven their antiviral effects through in vitro drug screening tests

Researchers have discovered a powerful drug candidate, methotrexate, which can inhibit viral replication

"The results indicate that the antiviral activity of methotrexate may be related to its ability to inhibit the interaction of certain RNA helicases with other key proteins," Varjosalo explained

Next step-animal experiments?

In future studies, these six drug candidates may be used in animal tests, such as mice or primates

"We have established a comprehensive virus-host protein interaction network to identify candidate proteins that can be used as targets for drug reuse

The research project of the covid-19 consortium led by the University of Helsinki was funded by the Finnish Academy of Sciences

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Magazine

Molecular systems biology

DOI

10.

Article title

Antiviral drug discovery based on sars-cov -2 host proteome interaction

Article publication date

1-November-2021