Crowdsourcing the design of a new molecule 

In early 2020, scientists at the Diamond Light Source laboratory in Oxford examined how the main protease of SARS-CoV-2 would bind to small molecules called ‘fragments’. They exposed the main protease to hundreds of these fragments, observing how some naturally bound to various sub-pockets within the protease’s larger cleavage site. Employing a technique called crystallography, the researchers could determine which fragments attached to the cavity, and precisely where and how each one binds.

But fragment binding alone is not enough to inhibit protease activity.

Scientists needed to find ways to link several of these fragments together and merge them into a larger molecule with the appropriate 3D shape matching the larger binding pocket – a complex, daunting task.

So, in March 2020, they put all their data online. A researcher from Weizmann Institute then published a tweet, calling on the community of medicinal chemists from all over the world to submit designs of molecules built from these fragments.

As the world entered lockdowns, hundreds of researchers were willing to help and spontaneously joined this collaborative effort, now named the COVID-19 Moonshot. The scale of this massively crowdsourced drug discovery effort was unprecedented.

‘We expected a few hundred submissions. We got more than 18.000,’ wrote Ed Griffen, Technical Director at MedChemica, recalling the early days of Moonshot. ‘Social media allowed us to share progress in real time with the widest possible community of researchers. Artificial intelligence enabled us to work faster on the molecular designs.’

The molecules proposed by the community – those that could be relatively easily synthetized and manufactured, at least – were soon tested at Diamond Light Source laboratory to see how strongly they bind to the protease.

‘To design the molecule with the best shape is a bit like trying hundreds of thousands of keys in a lock until you find one that fits. That’s why this collaborative approach was so successful,’ explained Annette von Delft, Head of Anti-Infectives at the Centre of Medicines Discovery, Nuffield Department of Medicine at the University of Oxford, and partner of the Moonshot initiative.

Building on the results from fragment merging, one compound, named DNDi-6510, was designed and progressed into advanced safety and pharmacokinetic studies. It ultimately failed due to unexpected, late-stage findings – attrition is very common in early-stage drug discovery, with approximately 90% of new pre-clinical drug candidates never reaching clinical studies. But researchers quickly found a solution: the molecular structure was redesigned, and a backup molecule from the same candidate series as DNDi-6510 passed all the tests and continues to progress.

Key data for this new molecule, called ASAP-0017445, was presented in early 2025. It shows promise not only against SARS-CoV-2 but also against Middle-East respiratory syndrome (MERS) and related coronaviruses. A true ‘broad-spectrum’ antiviral, the molecule was nominated by DNDi as a pre-clinical candidate in September 2025.

How to ensure the future antiviral medicine will be affordable and widely accessible?

From the very beginning, the goal of Moonshot and ASAP researchers has been to make sure their potential future treatment would be affordable and accessible to everyone who needs it, whatever their income or their location.  

‘Antivirals have shown to be very effective in reducing risk of hospitalization and deaths during the COVID-19 pandemic, but, as for vaccines, there were serious issues around access to the drugs in low- and middle-income countries. Humanity must not repeat the same mistakes,’  said Annette von Delft. 

In a pandemic emergency, lack of access to life-saving health tools costs lives. According to a modelling study published in Nature Medicine, more equitable access to vaccines during the COVID-19 pandemic could have prevented around 1.3 million deaths worldwide.  

This is why, in parallel with the development of broad-spectrum antivirals, and prior to patent filing, ASAP researchers agreed on contractual commitments and safeguards to ensure that their future treatments could be simultaneously produced by multiple pharmaceutical companies in different regions of the globe – hence making sure new medicines could be quickly made available everywhere, and at the lowest sustainable price. 

All these commitments are detailed in the ‘ASAP policy on intellectual property and open science disclosure’ – a document that is also public.