How to marshal a crowd to launch a moonshot against Covid-19

Anti-viral compounds offer the chemical equivalent of a rugby tackle to the ground. They are designed to intercept a virus before that hostile invader can hijack cell machinery to start replicating.

Now the global race is on to design a compound that can tackle Covid-19 into submission. One notable effort is the Covid Moonshot project: scientists working in universities and industry across the world have joined forces to crowdsource designs for a molecule in the hope of shortcutting a process that usually takes years. The non-profit endeavour has yielded more than 3,500 designs, with one compound already being hailed as a therapeutic possibility.

Covid Moonshot is managed by PostEra, a start-up company linked to Cambridge university that specialises in sifting through large data sets. It is also running a crowdfunding campaign to raise $2m for the research. The project, hosted at one the UK’s top science facilities and using crucial input from China and Israel, shows how scientists are finding fresh ways to raise their collective game against this global enemy.

The first step to sourcing an antiviral is to know the shape of the foe, and especially that of any weak spot. One component of the Sars-CoV-2 virus, which causes Covid-19, is called the main protease: this enzyme is critical to the virus being able to make new copies of itself. In other viruses, it is regarded as an Achilles heel. Protease inhibitors are known to be effective against HIV, for example. In January, researchers at Shanghai Tech University were able to find out exactly what the Sars-CoV-2 main protease looks like structurally, using a pure form of light called synchrotron radiation.

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When that radiation source was temporarily unavailable, the Shanghai researchers contacted the Diamond Light Source in Oxfordshire, UK, another synchrotron radiation facility. Diamond has now built a testing pipeline around the protease target.

The first step was to identify “fragments”, or simple molecules, that might attach to the protease. Many of these candidate fragments were proposed by the Weizmann Institute of Science in Israel. When one is added to the protease, synchrotron radiation can reveal distinctive “binding” signals. These hint that the fragment has managed to latch on and therefore could be a useful building block in any antiviral.

“We found about 80 fragments that showed strong signals of binding to the protease,” says David Stuart, director of life sciences at Diamond and professor of structural biology at Oxford university. “But these are just the first hints of what’s going on. The testing process generates a huge amount of information and the idea of the moonshot is to put it in the public domain. That allows chemists everywhere to look at the data and come up with ideas.”

This is where the crowdsourcing comes in. Chemists are being invited to design compounds using those fragments as a starting point, a challenge akin to playing chemical Lego. Good computational and experimental chemists, Prof Stuart says, might be able to spot common characteristics of binding hotspots in the Diamond data, which may lead to better designed molecules.

More than 3,500 designs have already poured in. Pharmaceutical companies have thrown in suggestions. Submissions are being “triaged” to prioritise those with simple structures, which are easier to manufacture at speed and scale. Enamine, a chemical company in Kyiv, is on standby to make candidate compounds for more advanced testing.

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Prof Stuart, whose usual research relates to the picornaviruses that cause diseases including foot-and-mouth, says Diamond has suspended all non-Covid research at its facility. “You’ve just got to try and hope you can do something that turns out to be useful.” He says: “This moonshot is allowing people to come together in a very open way.”

The ambition is to have several candidate compounds within months. A suite of potential antivirals — in case the virus develops resistance to a single treatment — would buy time for a vaccine, which is expected to take at least a year. Covid-19 may yet succumb to the chemical wisdom of crowds.

The writer is a science commentator



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