The Road Toward Clinical Trials With so many designs to choose from, the next step involved finding a way to whittle them down to create a shortlist of the most promising. The expertise of computational drug discovery experts at Diamond and the Weizmann Institute of Science in Rehovot, Israel, has enabled the Moonshot team to develop algorithms for predicting how quick and easy each one would be to make, and to predict how well each proposed drug might bind to the virus in practice. The latter is an approach known as computational covalent docking and has previously been used in cancer research. “This was becoming more popular even before COVID-19, with several covalent drugs approved by the FDA in recent years,” said Nir London, professor of organic chemistry at the Weizmann Institute, and one of the Moonshot team members. “However, all of these were for oncology. A covalent drug against SARS-CoV-2 will certainly highlight covalent drug discovery as a viable option.” This approach has whittled the submissions down to just 200. Over the past few weeks, the team has raised funding for the most promising of these – compounds which Lee has dubbed the ‘golden tickets’ – to be man- ufactured. This process is being partially financed by crowdfunding as well as contributions from research labs around the globe. Over the next month, each one will be put through a series of rigorous preclinical tests to make sure they are safe and to see whether they are effective at killing the virus in a test tube and in rodents. While it is still too early to begin planning clinical trials, the Moonshot team aims to have a prospective drug candidate by the end of the summer, allowing them to reach out to potential pharmaceutical part- ners to test their compounds in humans. Future Implications If the project does succeed, some believe it could open the door to scientific crowdsourcing as a future means of generating novel medicine ideas for other diseases. Frank von Delft, professor of protein science and structural biology at the University of Oxford’s Nuffield Department of Medicine, describes it as a new form of ‘citizen science.’
“There’s a vast resource of expertise and imagination that is simply dying to be tapped into,” he says.
Others are slightly more skeptical, pointing out that the uniqueness of the current crisis has meant that many scientists were willing to contribute ideas with- out expecting any future compensation in return. This meant that it was easy to circumvent the traditional hurdles which prevent large-scale global collabora- tions from happening – namely how to decide who will profit from the final product and who will hold the intellectual property (IP) rights. “I think it is too early to judge if this is a viable model for future drug discovery,” says London, the chemistry professor and member of the Moonshot team. “I am not sure that without the existential threat we would have seen so many contributions, and so many people and institutions willing to waive compensation and future royalties. Many scientists found themselves at home, frustrated that they don’t have a way to contribute to the fight against COVID-19, and this project gave them an opportunity. Plus many can get behind the fact that this project has no associated IP and no one will get rich off of this effort. This breaks down a lot of the typical barriers and red-tape for wider collaboration.” However the Moonshot team believes that if they can succeed, it will at the very least send a strong state- ment to policy makers and the scientific community that greater efforts should be made to enable such large-scale collaborations. “All across the scientific world we’ve seen unprece- dented adoption of open-science, collaboration and collegiality during this crisis, perhaps recognizing that only a coordinated global effort could address this global challenge,” says London. “If a drug would sprout from one of these crowdsourced ideas, it would serve as a very powerful argument to consider this mode of drug discovery further in the future.”
David Cox is a science and health writer based in the U.K.. He has a Ph.D. in neuroscience from the University of Cambridge and has written for newspa- pers and broadcasters worldwide including BBC News, The New York Times, and The Guardian.
How COVID-19 Could Usher in a New Age of Collective Drug Discovery
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