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The COVID Moonshot Partnership Presents: A Roadmap for Accelerated Drug Development and Coping with Future Pandemics

A tweet by Prof. Nir London from the Weizmann Institute of Science grew into an international partnership to find a cure for Corona based on the principles of open science and crowd wisdom. Now the scientists involved are laying the groundwork to deal with the next epidemic

March 2020: One by one countries close their doors and announce closures. The global economy and within it also academia and scientific research come to a screeching halt. Out of the stagnation and social distance was born an initiative designed to bridge distances and break boundaries - a non-profit partnership of researchers from all over the world to find a cure for the virus. More than three years later, this initiative is a partnership COVID Moonshot jointly led by prof. Near London From the Weizmann Institute of Science and researchers from the University of Oxford, from the Memorial Sloan Kettering Cancer Center and the American biotechnology company PostEra - presents a road map for accelerated drug development freed from intellectual property barriers - not only for Corona but for large groups of viruses from which the next epidemic may emerge. The findings of this unique partnership based on the principles of "open science" are widely published today in the scientific journal Science.

Shortly after the epidemic broke out, and in the midst of the international race to find an effective treatment for the virus, Prof. London and his colleagues in the world chose an unusual step: they shared online in real time all the findings that emerged in their laboratories in this regard for the benefit of the entire scientific community. "At a time of global crisis, this seems like a necessary step to us," recalls Prof. London, whose laboratory in the Department of Chemical and Structural Biology specializes in developing technologies to accelerate the discovery of new drugs, especially small molecules capable of blocking various protein activities.

Visualization of the XNUMXD structure of a key protein in the coronavirus: the main protease enzyme essential for its ability to replicate and thrive (marked in turquoise). The researchers were looking for molecules that could bind to different targets on the protein (marked in yellow) and thus block its activity. Source: Diamond Light Source
Visualization of the XNUMXD structure of a key protein in the coronavirus: the main protease enzyme essential for its ability to replicate and thrive (marked in turquoise). The researchers were looking for molecules that could bind to different targets on the protein (marked in yellow) and thus block its activity. Source: Diamond Light Source

Researchers from the University of Oxford and the United Kingdom's national synchrotron - Diamond Light Source - already deciphered the 80D structure of a key protein in the corona virus at an early stage of the epidemic: the main protease enzyme that is essential for its ability to replicate and thrive. Together with the British researchers, Prof. London searched for a molecule that would block the activity of this protein. The scientists identified about 80 compounds that could be a starting point for developing a cure for the virus. They teamed up with PostEra to use the artificial intelligence tool they developed to flag the most promising compounds among the XNUMX and search for additional compounds.

Things began to gather momentum when Prof. London posted a tweet on Twitter (now X) inviting the global scientific community to offer ideas to improve the identified compounds. The tweet gained hundreds of shares, and within a week Prof. London and his colleagues received more than 2,000 suggestions for improving the molecules. "Many scientists were in quarantine, just waiting for the opportunity to mobilize for a worthy cause," explains Professor London.

The cooperation kept expanding. A volunteer group of medicinal chemists led by Dr. Ed Griffin from the British biotech company MedChemica ranked the compounds according to their potential and continued to design new compounds; A research group from the Memorial Sloan Kettering Cancer Center in the US performed a computerized evaluation of them, and finally, a Ukrainian company called Enamine made a vital contribution by agreeing to produce the most promising molecules at almost cost prices.

Shipments of molecules from Ukraine began to arrive on the streets every week. Prof. London took them to the laboratories of the Israeli National Center for Personalized Medicine named after Nancy and Steven Grand, where they were tested using the most advanced biochemical scanning methods. The results obtained were shared online in real time, scientists from all over the world offered more suggestions for improvement - and God forbid. The optimization proceeded in this way for more than 50 rounds.

This is how the original collaboration grew into a much larger initiative that included many partners. This partnership, dubbed the COVID Moonshot, Received a $10 million research grant from the Wellcome Philanthropic Research Foundation. The scientists involved worked voluntarily, and all the data received was open in real time to the scientific community, without barriers of intellectual property, and without anyone having commercialization rights on the findings.

The original thought behind the project was that the pharmaceutical companies would be able to develop generic drugs based on the findings - that is, relatively cheap drugs that are not protected by a patent and therefore would be more accessible to poor countries and underprivileged populations. In fact, from an early stage a Swiss non-profit organization specializing in helping vulnerable populations - Drugs for Neglected Diseases Initiative (DNDi) - adopted the project and added it to its portfolio in the field of drug development.

In the end, the project produced more than 18 thousand possible compounds. More than 2,400 of its compounds have been actually produced, and more than 10,000 biochemical scans have been performed on them, and more than 500 compound structures have been solved in XNUMXD using X-ray crystallography. In a study published inScience A large space is dedicated to one of those compounds - a molecule that holds great promise for blocking the replication of the corona virus, and it works differently from the drugs currently on the market. The scientific article also shows that the findings of the partnership have already helped in practice to develop a new original drug: the drug for Corona Xocova (ensitrelvir) which received emergency approval in Japan in 2022 and was developed, among other things, based on the findings of the COVID Moonshot.

But perhaps the most significant achievement of the partnership is drawing a road map and creating an infrastructure to accelerate the search for drugs against many other viruses using the tools of "open science". In fact, the project leaders have already established Antiviral Drug Discovery Center who won the last for an initial grant of $68 million from the US National Institutes of Health (NIH). The research at the center is expected to deal with the identification of compounds from which drugs can be developed against three large families of viruses - the families from which the next epidemic may break out. Among these viruses is, for example, the Zika virus, which causes severe birth defects when it is passed from mother to baby during pregnancy.

"The COVID Moonshot is a great example that open science can be an effective alternative to the existing model of drug development," says Prof. London. "This approach is based on crowdsourcing and the removal of intellectual property barriers - and therefore has the ability to incredibly accelerate the development of medicines urgently needed by humanity."

Besides Prof. London, the study is also signed by Dr. Melissa Bobby and Prof. John Kudra from the Memorial Sloan Kettering Cancer Center; Dr. Darren Peron of Diamond Light Source; Dr. Matteo Perla, Dr. Lisabe Kokmuir, Dr. Annette von Delft and Prof. Frank von Delft from the University of Oxford; Michaelo Philip from the Weizmann Institute of Science; Dr. Matthew Robinson and Prof. Alpha Lee from PostEra; And about 200 more members of the COVID Moonshot partnership.