Stage 3
SPECIAL PRIZE - FIND AN IMMEDIATELY USABLE DRUG COCKTAIL | 80 DAYS (after validation of stage 1 and 2 – NOT OPEN YET)
The Moonshot: Using high-throughput viral assays and computational methods to immediately jump to drug-cocktails – a fast track to a Covid-19 therapy by skipping the “one disease, one drug” mantra.
The goal : Systems Medicine approaches are now available[1] and should rapidly be employed to find novel drug combinations with lower toxicity and off-target effects, which could rapidly be evaluated in clinical trials and provide immediate relief for the Covid-19 crisis.
Details:
Up to 1.000.000 Euros for the top-ranked team that experimentally screens combinations of FDA-approved compounds and demonstrates synergistic[2] effects. A minimum of 1000 different FDA-approved compounds need to be evaluated. The reduction of infectious SARS-CoV-2 virus yields should be >> 2-log in a standard multicycle growth assay (description and options for alternative assays as specified for Stage 2), preferably at sub-micromolar concentrations. Moreover, the most promising compound combination(s) identified by viral assays on cells should be evaluated in a relevant animal model at physiologically relevant doses, as compared to the appropriate negative control group, and sufficient statistics should be provided. Teams should demonstrate the relevance of the selected compounds and of their animal model to the human Covid-19 disease. Compound combinations should be used in a therapeutic manner (not prophylactic), and not show significant cytotoxicity in human cells. Evidence of significantly reduced disease severity versus a control group should be provided based on the monitoring of indicators such as weight loss, viral loads in the respiratory tract, pathology scores in the respiratory tract, and/or other indicators. Compounds can include, but are not limited to, aribidol, baricitinib, camostat mesylate, chloroquine (or derivatives), interferon-beta, lopinavir, remdesivir, ribavirin, sarilumab, or other FDA-approved compounds. Compound combinations that are already in use in human[3] for Covid-19 by the starting date of stage 3 are excluded (such as hydroxychloroquine + azithromycin, lopinavir + ritonavir, etc.).
We expect teams to adhere to local ethical and regulatory legislation (for EU[4]).
Stage 3 runs independently from stage 1 and 2, but outcomes of the previous stages can be used to identify FDA-approved compounds to be included in the screening of stage 3.
[1] http://doi.org/10.1126/scitranslmed.3006667 ; http://doi.org/10.1038/nbt.2391 ; http://doi.org/10.1093/bioinformatics/btw230
[2] Where the combined effect is greater than the sum of the individual effects
[3] See for example https://www.covid19-trials.com/
[4] https://ec.europa.eu/environment/chemicals/lab_animals/index_en.htm