Billion Molecules Against COVID19 Challenge

The Covid-19 major health crisis has highlighted the need for strong anticipation, interdisciplinarity and massive agility. The “Billion Molecules against COVID-19” Global Grand Challenge, led by JEDI with the support of the AXA Research Fund and Merck, was launched at the height of the COVID-19 health crisis. Its objective: to identify molecules capable of blocking SARS-CoV-2 by screening over one billion compounds using advanced computational methods and high-performance computing, followed by experimental validation.

Over 30 international teams participated to this first-ever DARPA-type (Advanced Research Projects Agency) challenge in Europe, leveraging artificial intelligence, molecular modelling, and virtual screening to propose hundreds of thousands of candidate molecules against key viral targets. The most promising compounds were synthesised and tested for their ability to inhibit viral replication or binding.

This unprecedented open-science initiative brought together expertise in epidemiology, structural biology, virology, and drug development, accelerating the path from virtual screening to potential therapeutic candidates — and laying the groundwork for faster responses to future pandemics.

The NLM article below details the results:

A community effort in SARS-CoV-2 drug discovery - PMC

Extract : Participating teams used a wide variety of computational methods to screen a minimum of 1 billion virtual molecules against 6 protein targets. Overall, 31 teams participated, and they suggested a total of 639,024 molecules, which were subsequently ranked to find ‘consensus compounds’. The organizing team coordinated with various contract research organizations (CROs) and collaborating institutions to synthesize and test 878 compounds for biological activity against proteases (Nsp5, Nsp3, TMPRSS2), nucleocapsid N, RdRP (only the Nsp12 domain), and (alpha) spike protein S. Overall, 27 compounds with weak inhibition/binding were experimentally identified by binding-, cleavage-, and/or viral suppression assays and are presented here. Open science approaches such as the one presented here contribute to the knowledge base of future drug discovery efforts in finding better SARS-CoV-2 treatments