CoviDrug-19

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  EUvsVIRUS with the CoviDrug-19 Team !

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  CoviDrug-19: final results (short list)

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  Example of in silico docking challenge of the best drug candidates to be repurposed

CoviDrug-19 for repurposing drugs!

Inspiration: In the context of the COVID-19 outbreak provoked by SARS-CoV-2, we have created a dream team able to use in silico tools to perform emergency research based on existing drugs repurposing. Indeed, since a lot of already marketed drugs can have unexpected positive side-effects, it seems relevant to explore them to repurpose these medicines against COVID-19! We assume that it is a convenient strategy through the availability of a marketed drug and the amount of accumulated knowledge, in particular concerning its safety.

About the tool: Our team is composed of two pharmacists specialized in drug discovery and an IT manager. With these complementary skills, we developed a hybrid approach based on a critical analysis of scientific literature regarding the COVID-19 outbreak and the use of a high throughput tool dedicated for virtual screening of molecules. For the basis of this project, we identified three major SARS-CoV-2 targets: the main and papain-like proteases and the helicase. Then, we explored molecules / drugs databases in order to construct a chemical library of about one thousand candidates (based on pubchem and drug bank). Then, we used a virtual screening software (PyRx®) able to compute the interaction of a given chemical library with a biological target. We performed this workflow for each target and obtains values of binding affinity for each molecule (the more negative the value, the better). Quality control of the results was performed with a manual docking of the best candidates into their respective targets. Thus, through this global approach, we identified a potential drug library of about 50 molecules, including a majority of already marketed drugs (antiviral drugs against hepatitis C & HIV).

During the EUvsVIRUS Hackathon: The teams of pharmacists performed literature analysis, selection / modelization of the targets, and building of the chemical library while IT manager performed debugging and the virtual screening of several chemical libraries with PyRx. Part of the results was submitted to the team's mentor, specialized in drug repurposing. We took into account some of its advice to study an experimental patented drug against the helicase of SARS-CoV-2. This approach made it possible to explore virtually a part of the chemical space to see if an already similar structure might be already marketed, what was not the case. At last, complementary skills within the team allowed us to produce three listings of drugs against our three SARS-CoV-2 targets.

Potential impacts on the crisis: Given the suddenness of the outbreak and the lack of specific therapies against COVID-19 caused by SARS-CoV-2, we assume that all strategies dedicated to drug repurposing should increase the resilience of countries. Thus, drug repurposing strategies should favor in silico approaches which are fast while maintaining a high level of relevance.

What's next for CoviDrug-19 We would like to work with key opinion leaders in infectious diseases and pharmaceuticals companies, in order to convince them to perform clinical trials aiming for the repurposing of the drugs we identified in the field of COVID-19.

Built With

• databases
• drugbank
• drugs
• molecules
• pubchem
• pyrx
• screening
• virtual