A consortium led by international scientists from the non-profit, open-science COVID Moonshot, of which Diamond is a member, has been awarded an initial $68 million from the US National Institutes of Health (NIH) to discover and develop globally accessible and affordable novel oral antivirals to combat COVID-19 and future pandemics.
The new consortium, named AI-driven Structure-enabled Antiviral Platform (ASAP), builds on the cutting-edge technologies that drove the COVID Moonshot, encompassing advanced structural biology, AI, machine learning, and computational chemistry on Folding@home, the world’s largest distributed computing platform, to build a robust antiviral discovery pipeline.
Demonstration of data processing at Diamond’s XChem facility looking at the structure of SARS-CoV-2 Mpro. Copyright Diamond Light Source.
ASAP is one of the Antiviral Drug Discovery (AViDD) Centers for Pathogens of Pandemic Concern funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) as part of the Antiviral Program for Pandemics (APP). Today’s award (award number 1U19AI171399-01) is for the initial three-year phase of the ASAP project, which aims to produce multiple drug candidates, ready for evaluation in humans, against multiple viruses of pandemic potential.
Frank von Delft, Professor of Structural Chemical Biology at the University of Oxford, Principal Beamline Scientist at Diamond Light Source, co-founder of the COVID Moonshot and a Principal Investigator in ASAP explains:
It is deeply sobering that the drugs that could have saved many millions of lives by halting COVID in its tracks right back in 2019, could already have been developed by 2010. The AViDD Centers are a push to not repeat this mistake, and through ASAP, we can help build the stockpile of antiviral compounds that, by being affordable and equitably accessible, will nip the next pandemic in the bud.
The COVID Moonshot is a spontaneous global collaboration that started in March 2020, triggered by data from Diamond’s XChem platform for fragment screening, and rapidly identified potent antivirals targeting the main protease of the SARS-CoV-2 virus. These antivirals are now undergoing a preclinical programme funded by the Wellcome Trust; moreover, the data openly shared by Moonshot additionally enabled the identification of another promising COVID-19 drug developed by the Japanese pharmaceutical company Shionogi that is now in late-stage clinical trials.
Dr Alpha Lee, Chief Scientific Officer of PostEra, co-founder of the COVID Moonshot and one of the leaders of ASAP said:
The rapid progress of Moonshot demonstrates the power of AI-driven drug design. Our algorithms generate molecules with optimised properties that can quickly be made and tested in the lab, and help us select the most important experiments. ASAP will take this to the next level.
Diamond leads the ASAP activity that readies individual viral proteins for the ASAP technologies of rapid drug design. Moreover, Diamond’s XChem platform provides a pivotal role in accelerating the so-called design-make-test cycles that drive drug discovery. Through its world-leading ability to measure X‑ray diffraction data from up to 1000 protein crystals in a day, it not only generates detailed 3D views of how the designed compounds interact with the proteins of interest, but does so comprehensively, for all designed compounds, thus greatly enhancing the efficiency of subsequent rounds of compound design.
Prof. Frank von Delft said:
ASAP is a unique opportunity to achieve a step-change both in the antiviral field and in the methodologies of drug discovery. On the one hand we can fully develop our transformative techniques so that they become widely available and used. Even more importantly, we will generate huge amounts of highly accurate and meticulously curated data, that will be made immediately available – an unprecedented resource that will underpin the next generation of computational tools for drug design that will transform in the efficiency of drug discovery.
ASAP will target viral families that have been historically neglected by the market, with an initial focus on coronaviruses, responsible for the current COVID-19 pandemic as well as earlier SARS and MERS epidemics. It will also address flaviviruses, responsible for large endemic diseases such as dengue and Zika whose vectors will inevitably come to the United States due to climate change; and picornaviruses, responsible for devastating diseases such as polio.
ASAP is led by the Memorial Sloan Kettering Cancer Center (USA), PostEra (USA), and the Drugs for Neglected Diseases initiative, DNDi, (global). The other partners are Diamond Light Source (UK); the Weizmann Institute of Science (Israel); Medchemica (UK); Mount Sinai (USA); Stanford University School of Medicine (USA); the Fred Hutchinson Cancer Center (USA), and a vast global network of scientists and industry collaborators.
Rachel Cohen, Regional Executive Director of DNDi North America concluded:
We are honored to be a part of this consortium and to be receiving support from NIAID, especially because ASAP is prioritising open sharing of research knowledge and data and delivery of novel therapeutics with the explicit goal of ensuring equitable access globally. There will be billions spent globally on discovery and development of new health tools for COVID-19 and other pandemics and we need new approaches like this so we can prevent the equity failures of COVID-19.
More details on ASAP and its mission can be found at http://asapdiscovery.org
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
Copyright © 2022 Diamond Light Source
Diamond Light Source Ltd
Harwell Science & Innovation Campus
Diamond Light Source® and the Diamond logo are registered trademarks of Diamond Light Source Ltd
Registered in England and Wales at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom. Company number: 4375679. VAT number: 287 461 957. Economic Operators Registration and Identification (EORI) number: GB287461957003.