Crowdsourcing powers early discovery for SARS-CoV-2

Celebrating World Science day during November, a study has emphasised the success of the COVID Moonshot Consortium’s use of crowd sourcing and Open Science to accelerate its discovery of both a potent SARS-CoV-2 antiviral lead compound and the launch  of a patent-free antiviral discovery program for rapid lead development in response to a pandemic emergency.     

Triggered by a Twitter appeal, COVID Moonshot started as a spontaneous virtual initiative in March 2020,  attracting  more than 200 scientists and students from academia and biopharma to join forces in an unprecedented, fully open collaboration, which rapidly identified and developed novel compounds with excellent antiviral activity against a key enzyme of the SARS-COV-2 virus, namely the main protease (Mpro). The candidate, a non-covalent, non-peptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors, is now in pre-clinical evaluation in collaboration with the Drugs for Neglected Disease initiative (DNDi).

Leveraging machine learning, exascale molecular simulations and high-throughput structural biology and chemistry and Diamond Light Source’s XChem facility for crystallographic fragment screening, the team were able to generate a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes and a wealth of biochemical activity data, which shared openly, created a rich open and IP-free knowledge base for future anti-coronavirus drug discovery.

By making all data immediately available, with all compounds purchasable from the Ukrainian chemistry supplier Enamine, the consortium aims to accelerate research globally along parallel tracks following up on their initial work.  “The data set enclosed in the Science publication provides a unique resource linking comprehensive structural data, fragment hits, multiple chemical scaffolds, as well as biochemical and cellular assay data that can be viewed and exploited by other scientists”, said Dr Lizbe Koekemoer, a lead author and team leader at the Centre for Medicines Discovery, University of Oxford. 

Dr Annette von Delft, University of Oxford adds; “This publication showcases the enormous value that crowd-sourcing can bring to drug discovery. The COVID Moonshot project has been unique in its collaborative approach and commitment to open science and demonstrates how collaboration can be a driver for innovation.”

“Every day at Diamond, we are proud to be working with leading scientists and academics from all over the world like the COVID Moonshot Consortium, who are conducting innovative and inspired research using our facility. Bringing together experts in physical and life science innovations, cross disciplinary teams, and access to collaborative facilities allows our users to shine their brilliance on new technologies, treatments, sustainable materials and climate solutions for the many 21st century challenges we face,” comments Diamond’s new CEO, Gianluigi Botton.

The discovery platform collaboration that spontaneously formed as the COVID Moonshot now continues its work as the ASAP discovery consortium, which stands for AI-driven Structure-enabled Antiviral Platform, aiming to discover and develop novel broad-spectrum small molecule inhibitors against coronaviruses, flaviviruses and enteroviruses for pandemic preparedness.

The initiative is a collaborative effort of the Nuffield Department of Medicine at the University of Oxford; Diamond Light Source; PostEra; Weizmann Institute of Science; MedChemica Ltd; Icahn School of Medicine at Mount Sinai; Enamine Ltd; Memorial Sloan Kettering Cancer Center; and Thames Pharma Partners LCC.

 Covid Moonshot paper: Open Science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors DOI 10.1126/Science.abo.7201

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