The COVID Moonshot initiative started as a spontaneous virtual collaboration in March 2020. It is a non-profit, open-science consortium of scientists from around the world dedicated to the discovery of globally affordable and easily manufactured antiviral drugs against COVID-19 and future viral pandemics.
With the help of more than 200 scientists worldwide, novel compounds with excellent antiviral activity against the main protease of SARS-CoV-2 were identified. The lead candidate is now in pre-clinical evaluation in collaboration with the Drugs for Neglected Disease initiative (DNDi).
The initiative is a collaborative effort of the Nuffield Department of Medicine; 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.
Key drivers of the COVID Moonshot effort at NDM’s Centre for Medicines Discovery (CMD) were the first authors of the study, Lizbe Koekemoer and Matteo Ferla, as well as Professor Frank von Delft, and Dr Annette von Delft; together with many other collaborators across multiple departments of the University of Oxford.
The discovery platform collaboration that spontaneously formed as the COVID Moonshot now continues its work as the ASAP discovery, 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 research paper was published in the Science journal.
Dr Annete von Delft, Translational Scientist at CMD said: ‘This publication showcases the enormous value that crowd-sourcing can bring to drug discovery. COVID Moonshot project has been unique in its collaborative approach and commitment to open science, and demonstrates that collaboration can be a driver for innovation.’
Dr Koekemoer, Postdoctoral Scientist and a team leader at the CMD, adds: ‘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.’
John Chodera, laboratory head at the Sloan Kettering Institute at the Memorial Sloan Kettering Cancer Center, said: ‘COVID-19 has killed more than 1.1 million people in the United States, disabled millions more, and caused over $14 trillion in damage. We can’t afford to be caught unprepared by the next pandemic. The COVID Moonshot produced antivirals that were equipotent against SARS-CoV-1, suggesting there’s no reason we couldn’t have done this for just a few million dollars in 2006. We urgently need to invest in oral antiviral discovery now so we can have the tools we need to halt pandemics before they start.’
Prof Nir London of the Weizmann Institute of Science, said: ‘This collaboration demonstrates an alternative model for drug discovery. By building on the strength of numerous contributors and removing red-tape, it can tremendously speed up the discovery of drugs urgently needed to avert global threats.’
Mihajlo Filep, PhD student at Weizmann Institute of Science, said: ‘By joining forces, we successfully ran an extensive drug discovery campaign within the academic circles, with an emphasis on utilizing high-throughput methods to rapidly diversify hit compounds and evaluate SAR (structure-activity relationship).’
For more information on the project, visit https://dndi.org/research-development/portfolio/covid-moonshot/
Read full paper here: Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors | Science