On Wednesday 18th May the NIH announced that the team that led the COVID Moonshot, including ourselves at MedChemica, along with additional collaborators has been awarded an initial $68 million to discover and develop globally accessible and affordable novel oral antivirals to combat COVID-19 and future pandemics caused by RNA viruses. The award is for the initial three-year phase of the five-year AViDD Center. At MedChemica we’ve been part of the COVID Moonshot team for the last two years, coordinating the Lead Optimization efforts and we’re building on that in the new ‘AI-driven, Structure-enabled Antiviral Platform (ASAP)’ consortium. Among the many tragedies of the COVID-19 pandemic, not the least is that if we’d had a diverse stockpile of potential drugs built on the learning available from the SARS epidemic of 2002, we could have potentially saved millions of lives and huge amounts of misery world-wide. What we need for the future is to have a range of early-stage compounds ready to put immediately into trials as soon as a future pandemic arises. Those drugs then need to be affordable and equitably accessible to everyone. Among the learnings from COVID-19 is that viral pandemics respect no borders; we will need to get the drugs to the places outbreaks occur and scale up supply to suppress a pandemic as quickly as possible.
When I joined the COVID Moonshot in March 2020, in the heat of the early pandemic, we dived into generating leads and optimizing them with every tool at our team’s disposal. The COVID Moonshot is a global, open-science collaboration and we have identified potent antivirals targeting the main protease of the SARS-CoV-2 virus, which are currently progressing through a preclinical program funded by the Wellcome Trust / COVID-19 Therapeutics Accelerator. The open science data publicly shared by Moonshot additionally enabled the identification of another promising COVID-19 drug developed by the Japanese pharmaceutical company Shionogi (Ensitrelvir) that is now in late-stage clinical trials.
The team we built in the Moonshot has achieved a huge amount incredibly rapidly and, as our lead compound progresses towards human trials, we’ve reflected on what we’ve learnt and looked at what we can put into practice to prepare for a future pandemic. Our structural biology team and fragment-based lead generation approach has delivered outstanding numbers of protein-ligand crystal structures (over 800 to date). Using artificial intelligence (AI), machine learning, computational chemistry on Folding@home as well as a huge amount of hard synthesis and biological testing, we have compounds with good activity and pre-clinical pharmacokinetics being progressed. We’ve taken everything we’ve learnt and enhanced it. Our compound and data logistics were good, now we’re stepping up a gear to go after more projects and a multi-year program of work. Most of us have worked together as a team for 2 years, often in highly challenging and unusual circumstances, including the war in Ukraine. We’ve now welcomed on board more virologists to ensure we work on the right biological targets and improved our testing capabilities to give the best chances of heading the next pandemic off earlier. Partners in the ASAP Center include the Diamond Light Source (UK); PostEra (USA); the Memorial Sloan Kettering Cancer Center (USA); the Weizmann Institute of Science (Israel); Mount Sinai (USA); Stanford University School of Medicine (USA); the Fred Hutchinson Cancer Center (USA), and the Drugs for Neglected Diseases initiative (global), and of course ourselves at MedChemica as well as a vast global network of scientists and industry collaborators.
ASAP will be one of the Antiviral Drug Discovery (AViDD) Centers funded by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) as part of the Antiviral Program for Pandemics (APP). We are targeting viral families that are known threats but have been neglected by more market driven approaches including coronaviruses (responsible for the current COVID-19 pandemic as well as earlier SARS and MERS epidemics), flaviviruses (responsible for large endemic diseases such as Dengue and Zika whose vectors will inevitably move north due to climate change), and picornaviruses (responsible for devastating diseases such as polio).
We have a real sense of pride in MedChemica in being able to play our part in this consortium. We will be bringing the best of what we do to prepare for the next pandemic and in particular to make sure there are potential drugs ready for human testing when it comes, because we really mustn’t be caught like that again.
More details on ASAP and its mission can be found at http://asapdiscovery.org