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Stage 1

ULTIMATE LIST OF LEAD COMPOUNDS BY SCREENING A BILLION MOLECULES AGAINST  COVID-19 | 33 DAYS

The Moonshot: Test molecules against SARS-CoV-2 at a scale never seen before by computational screening of enormous libraries against high-resolution protein structures using supercomputing and potentially machine learning. Use cross-correlation of results within and among teams to determine a “high potential” compound list of unprecedented quality: a fast track to clinical testing. The overall time to find active compounds reliably will be massively shorter when compared to that of current methods.


The goal : In this stage we aim to improve the accuracy of simulations by adopting an approach that has successfully been applied by climate scientists. That is, different simulation approaches are compared to one another and in this way errors in assumptions are averaged out. The remaining “ultimate list” of compounds for each protein target can then quickly be screened experimentally and will be made available publicly.

Details:

  • 250.000 Euros for the top-ranked team or consortium that uses three independent computational methods to select from a library of > 1 billion compounds and provide a consensus list[1] of the top 10.000 lead compounds (ranked by affinity) for at least 3 Covid-19 targets[2]that are involved in viral entry or replication. Computational methods may include, but are not limited to, molecular dynamics, deep learning, deep docking, virtual flow, etc., and should consider ADME-Tox[3] qualities where possible. The screened compounds must include known FDA-approved compounds[4] and can optionally consider biologicals. The aim is to find good binders with < 100 nM affinity. If needed, teams will be asked to provide additional data or clarifications.

  • Strong evidence of reproducibility, such as publicly-available source code and/or submission to a peer-reviewed journal is desirable. Rapid open-access sharing without embargo periods, for example via preprint servers, is requested. Available experimental data4,[5] should be taken into consideration.

  • Teams need to show that the relevance and quality of protein targets are the highest possible and need to use the largest compound libraries available (by merging existing libraries). See our resources page.

  • An “ultimate list” will be compiled for each protein target and will consist of (up to) 10% of cross-correlated compounds across teams (depending on overlap of the lists), and 90% of top-ranked compounds from each team’s list. To ensure fair competition, an equal number of compounds from each team will be used. This ultimate list will be made available commercially as a physical library by our partners (for example as a DMSO stock), taking into account synthetic feasibility. The winning team has the highest score of compounds on the ultimate list(s), where score = (number of compounds)*(1/Kd); threshold = 1e7 M.

  • The dissociation constants of compounds on each ultimate list will be measured experimentally by our partners. Only compounds that can be reasonably made and targets that can be readily obtained will be considered. The program manager and the scientific committee will judge whether a team/consortium has satisfied the conditions for the prize to be awarded. If needed, teams will be asked to provide additional data or clarifications.



[1] Consensus list: a list of compounds that come out of each of the three different methods (i.e., cross-correlated). The format to be provided is *.csv using the template provided on http://covid19.jedi.group.

[2] Make sure to use high-quality protein targets. See for example: http://insidecorona.net ; http://covid.molssi.org . Consider glycosylation: https://doi.org/10.1016/j.bbagen.2019.05.012

[3] https://en.wikipedia.org/wiki/ADME

[4] Including at least the SWEETLEAD library (https://simtk.org/projects/sweetlead) , and expanded with as many (FDA-approved) molecules as possible.

[5] For example: https://www.diamond.ac.uk/covid-19/for-scientists/Main-protease-structure-and-XChem.html

 

Templates for submission

Download Now

Template for report (*.docx)

Please use this Word template to describe your methods, libraries, target, etc.

Template for consensus list (*.csv)

Please use this templates for your lists of compounds. Use 1 list for each protein target.

 

Submit here by 17 July 18:00 CET

Please access the submission page after agreeing to the Charter on the button below

JEDI GRANDCHALLENGES CHARTER​

The Joint European Disruptive Initiative (JEDI) is a major initiative to advance scientific and technological frontiers, for the greater good of humanity.

JEDI is launching GrandChallenges to push the frontiers of knowledge, with a strong objective of not only advancing science, but ensuring that breakthroughs are consistent with humanistic values and benefit as many people as possible.

When participating to a GrandChallenge, or by working with JEDI, we therefore ask participating teams (‘Performers’) and partners to adhere to following principles in addition to specific GrandChallenge rules & regulations found on JEDI websites, or updates thereof.

  • JEDI GrandChallenge are focused on major breakthroughs and disruptive science and technology, therefore JEDI, the Scientific Committees and the Program Managers retain full authority and flexibility on the process, evaluation, and total discretion to whom they allocate a prize, and whether they allocate a prize or not.

  • JEDI will bear no responsibility whatsoever, nor has any obligation to detail or explain the reasons for its choices when selecting winning teams to the GrandChallenges.

  • JEDI will support strong cooperation around the most promising results, and work with Performers on  individual and group publications. For efficiency reasons, Performers commit to wait for the first evaluation stages and not publish nor communicate any result before September 18

  • In any case, Performers will coordinate with JEDI before any communication or publication regarding work in the framework of the JEDI GrandChallenge


  • Performers share JEDI’s goal of having impact for humanity and are providing their work and results without conditions nor cost, and with no other goal than advance science. Performers agree to potentially have their results disclosed in the spirit of Open Science.

  • Performers confirm that no patent has been filed, or is currently being or planned to be filed on the compounds submitted to JEDI. Performers will inform JEDI without delay of any change of status

  • In order to ensure impact of the collective work produced during a GrandChallenge, JEDI may use various measures to disclose and/or to protect the work of Performers, like posting all or parts of their results on a public repository, ensure the right of priority in order to protect intellectual property at a later date, or agreements with institutions ready to commit time and resources to transform results into tangible progress for mankind.


I hereby, for myself and for the team I represent, support and fully agree with the JEDI GrandChallenges Charter.

 
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