Close Menu
    Facebook X (Twitter) Instagram
    Facebook Instagram Threads
    Global BiodefenseGlobal Biodefense
    Subscribe
    • Featured News
    • Funding
    • Directory
    • Jobs
    • Events
    Global BiodefenseGlobal Biodefense
    Medical Countermeasures

    COVID Moonshot Consortium Announces Crowd-Sourced Small Molecule Discovery

    The newly published work of the COVID Moonshot Consortium details discovery of a potent SARS-CoV-2 antiviral lead compound.
    By Global Biodefense StaffNovember 11, 2023
    Six people pose in front of banners for the COVID Moonshot Consortium participating organizations.
    Collaborators of the COVID Moonshot Consortium. Credit: Diamond Light Source
    Share
    Facebook LinkedIn Reddit Email

    The COVID Moonshot initiative started as a spontaneous virtual collaboration in March 2020, when a group of scientists and students from academia and biopharma, triggered by a Twitter appeal, joined forces to begin a race against the clock to identify new molecules that could block the SARS-CoV-2 virus.  This unprecedented, crowdsourced, and fully open collaboration of more than 200 scientists, 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 lead candidate is now in pre-clinical evaluation in collaboration with the Drugs for Neglected Disease initiative (DNDi).

    The COVID Moonshot is dedicated to the discovery of safe, globally affordable antiviral drugs against COVID-19 and future viral pandemics, and is pioneering a straight-to-generic, patent-free approach.  

    The consortium’s paper reports on the discovery of a non-covalent, non-peptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Their approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry.  It built on data from a large experiment, performed in record time at the start of the pandemic, at Diamond Light Source’s XChem facility for crystallographic fragment screening using Diamond’s high-throughput crystallography.  In the experiment, 1,495 fragment-soaked crystals were screened within weeks to identify 78 hits that densely populated the enzyme’s active site. 

    Male scientist wearing khaki shorts peers at large metal machines with lots of tubes and industrial piping in the background
    Professor Frank von Delft, Principal Beamline Scientist, Diamond 104-1. Credit: Diamond Light Source

    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. All compound designs (>18,000 designs), crystallographic data (>840 ligand-bound X-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2,400 compounds) for this campaign were shared rapidly and openly, creating a rich open and IP-free knowledge base for future anti-coronavirus drug discovery. 

    By making all data immediately available, 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”, states Dr Lizbe Koekemoer, one of the lead authors and a team leader at the Centre for Medicines Discovery, University of Oxford.   

    “This is the first time such a large number of protein-ligand structures have been generated for a drug discovery campaign and released in the public domain.  It is a testament to Diamond’s high-throughput crystallography infrastructure, but also the astonishing coordination across many research groups world-wide under enormous pressure”.

    Dr. Daren Fearon, co-lead author and Senior Beamline Scientist at Diamond Light Source, who leads the XChem facility.  

    As a striking example for the impact of open-science, the Shionogi clinical candidate S-217622, which is available in Japan under emergency approval as Xocova [ensitrelvir], was identified using the data generated at Diamond and openly released.  Senior author Prof Frank von Delft, Principal Beamline Scientist at Diamond, Professor for Structural Chemical Biology at University of Oxford, and one of the founders of the consortium, comments, “Open science efforts have transformed many areas of biosciences. The COVID Moonshot provides an exemplar of a viable route to open science early drug discovery leading to advances in infectious diseases drug discovery—a research area of grave public importance but one which is chronically underfunded by the private sector. The Moonshot structure-enabled drug discovery campaign targeting the coronavirus main protease is providing a roadmap for the potential development of future antivirals.”   

    “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.” 

    Dr. Annette von Delft, University of Oxford

    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. 

    Aerial view of Diamond Light Source. Credit: Diamond Light Source

    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.

    For more information on the project, visit COVID Moonshot.

    Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors. Science, 10 Nov 2023.

    Biotechnology COVID-19 Drug Discovery Editor Pick
    Share. Facebook LinkedIn Reddit Email
    Previous ArticleWHO Updates Guidance on Treatments for COVID-19
    Next Article NanoViricides’ Phase 1 Broad-Spectrum Antiviral Highly Effective for Mpox and Smallpox

    Related Stories

    First Light Diagnostics Receives FDA Clearance for Rapid Anthrax Test

    December 5, 2023

    Chlorine Exposure Biomarkers in a Large Animal Model

    December 5, 2023

    ARPA-H Announces New Tiered Proposal Submission System to Reduce Applicant Barriers

    December 5, 2023

    Human BCG Challenge Model for Assessment of Tuberculosis Immunity

    December 2, 2023
    News Scan

    Biodefense Headlines – 30 November 2023

    News Scan November 30, 2023

    News highlights on health security threats and countermeasures curated by Global Biodefense This week’s selections include the largest ever outbreak of mpox in the DRC; launch of National Wastewater Surveillance Program dashboard; low uptake of COVID-19 boosters and flu vaccines;…

    Upcoming Events

    Mar 12
    Hybrid Hybrid Event
    March 12, 2024 - March 17, 2024

    2024 Fungal Genetics Conference

    Mar 21
    March 21, 2024 - March 23, 2024

    ASPPH 2024 Annual Meeting

    View Calendar

    Subscribe to Global Biodefense

    Get the latest news on pathogens and preparedness

    News on pathogens and preparedness for public health emergencies

    © 2023 Stemar Media Group LLC
    • About
    • Contact
    • Privacy
    • Subscribe

    Type above and press Enter to search. Press Esc to cancel.