Stage 2
IDENTIFY COMPOUNDS THAT LEAD TO 99% VIRAL SUPPRESSION | 33 DAYS (after validation of stage 1 – NOT OPEN YET)
The Moonshot: From proven binding (stage 1) to proven viral suppression in a record time. Use the collective knowledge of virologists to pick and evaluate promising compounds from the ultimate lists to achieve excellent viral inhibition.
The goal: In this stage we aim to obtain hard evidence of compounds that can suppress live SARS-CoV-2 virus in cell assays. Teams can either do selective testing, high-throughput screening of thousands of compounds from the ultimate lists, or use smart combinatorial methods.
Details:
250.000 Euros for the top-ranked team/consortium that experimentally demonstrates the highest suppression of viral replication as compared to appropriate controls for at least one compound that they have selected from one of the ultimate lists (stage 1) or any other known compound or combination of compounds. The aim is to reach at least a 2-log reduction of infectious SARS-CoV-2 virus yields in a standard multicycle growth assay (PFU/mL titers measured at 48 hours post-infection in the supernatant of VeroE6 cells infected at 0.01 PFU/cells) at submicromolar total compound concentrations. Other viral assays can be used8 but a read-out equivalence with the standard multicycle growth assay should then be provided. Experimental results should include dose response curves for at least 100 compounds from the ultimate lists in total. Compounds should be used at physiologically relevant doses, in a therapeutic manner (not prophylactic), and not show significant cytotoxicity in human cells. Viral assays should be performed on relevant cell lines (preferably of human origin) and may include, but are not limited to, viral growth kinetics[1] and/or plaque reduction assays. The top compounds may optionally be evaluated in a relevant animal model, based on monitoring of weight loss, viral loads in the respiratory tract, pathology scores in the respiratory tract, and other relevant indicators.
We encourage teams to share proteins/constructs/compounds/methods publicly as much as possible.
Partial submissions using radically new approaches may also be considered.
If structural protein-compound data is generated during the process it needs to be deposited in the publicly accessible Protein Databank.
[1] We encourage the use of cell lines of human origin and the use of rapid screening using reporter-protein expressing SARS-CoV-2. For example: http://doi.org/10.1016/j.chom.2020.04.004