In fast lane for drug discovery

To date, no specific vaccines or antiviral drugs have been developed for SARS-CoV-2. Drug discovery is hindered by the fact that viruses do not have their own metabolism, but are dependent on the host. Researchers from the Universities of Helsinki and Eastern Finland tackle the task by identifying molecules (drugs) that would interfere with replication of the SARS-CoV-2 virus.

Last November (2019) infections of a new kind of coronavirus were announced but no one could have then anticipated how large an impact this new virus, SARS-CoV-2, would cause globally only a few weeks after its discovery. Now SARS-CoV-2 has spread around almost every place on Earth, with more than half a million victims. The current, best, COVID-19, patient treatment strategy is purely supportive.

In the project, a consortium (CoVIDD) led by Academy Research Fellow Markku Varjosalo, three groups from the University of Helsinki (Varjosalo, Research Director Petri Auvinen and Professor Sarah Butcher) and a group from the University of Eastern Finland (Professor Antti Poso) plan to tackle the task by identifying molecules (drugs) that would interfere with replication of the virus. Members of the CoVIDD consortium cover different disciplines from virology, genetics and interactome proteomics, to structural biology and drug discovery.

The newly formed consortium uses a multidisciplinary approach to test existing drugs that are already permitted for use in humans, or drugs that have been tested in clinical trials but found to be ineffective for their intended use.

“SARS-CoV-2 infection dramatically alters the intracellular environment of host cells to both enable virus replication and spread. However, relatively little is understood about how these viral proteins interact with the cellular factors and the host pathways involved. To effectively search for drugs that could modify viral replication we need to know which/how human proteins and viral proteins interact. Thus, a comprehensive virus-host protein interaction network will help us to identify the potential protein targets for screening repurposable drugs,” says Academy Research Fellow Markku Varjosalo from the University of Helsinki.

This is followed up with atomic-level structural determination of those interactions. Researchers then utilize the target protein structural data to virtually screen both clinically-approved drugs and the large libraries of compounds that have entered Phase I-III trials over the past 40 year in clinical studies. Researchers streamline this repurposing to exclude pharmacologically inaccessible targets, before going into cell-based virus inhibition assays that we have established in human cell lines. Hits could be taken in to animal testing, such as mice or primate, in a future study.

“Repurposing existing drug molecules is considerably faster than developing completely new molecules. However, we are also using those compounds which have not been effective in the intended use but are still safe enough to be used in SARS-CoV-2 infection. In addition, fast structural determination and world-class supercomputing facilities by CSC makes this project unique and likely successful,” says Sarah Butcher.

“As time is of the essence, we will promote much faster progression into clinical studies and potential antiviral therapy than normal brute force in vitro drug discovery approaches,” concludes Varjosalo.

See also news about Academy of Finland funding for Covid19 research:

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