COVID Moonshot’s groundbreaking research introduces new nonpeptidic inhibitors for SARS-CoV-2, showcasing global collaboration and open science in advancing coronavirus therapeutics.
Although the group’s work has been freely available since its inception in March 2020, the COVID Moonshot Consortium is finally formally reporting its results. The COVID Moonshot – an open-science, crowdsourced, and patent-free drug discovery campaign targeting the SARS-CoV-2 virus – has yielded a wealth of data on the virus’s main protease, including insights that could pave the way for the development of new and better therapeutics.
“The lead therapeutics described by [these researchers] may not be ready in time to affect the current pandemic, considering the timelines and challenges of drug approval,” write Brian Shoichet and Charles Craik in a related Perspective. “Nevertheless, the compounds and the techniques used to identify them may well affect human health in the future.”
Global Collaboration and Drug Discovery Efforts
The novel collaboration included more than 200 volunteer scientists from 47 academic and industrial organizations spanning 25 countries. “The COVID Moonshot provides an example of open science drug discovery leading to advances in infectious diseases drug discovery – a research area of grave public importance, but one that is chronically underfunded by the private sector,” write Melissa and colleagues.
Due to its essential role in viral replication, the SARS-CoVB-2 main protease (Mpro) is an attractive target for antiviral development. Current SARS-CoV-2 Mpro inhibitor drugs, such as those drawn from preexisting antiviral pipelines like Paxlovid and Xocova, have shown clinical success. However, the use of these compounds has remained relatively limited and their peptidomimetic and covalent scaffolds create issues for synthesis and administration.
Innovative Drug Design and Open Science Impact
Here, Boby et al. describe the discovery of a novel, noncovalent, and nonpeptidic inhibitor scaffold that is chemically distinct from current Mpro inhibitors. Leveraging a crowdsourcing approach and the combined expertise of hundreds of individuals worldwide, Boby et al. describe their open-science drug discovery campaign, which included machine learning, molecular simulations, and high-throughput structural biology and chemistry to assemble a detailed structural map of the SARS-CoV-2 main protease and its biochemical activity.
Of the more than 18,000 compound designs produced by the COVID Moonshot Consortium, the authors identified several noncovalent, nonpeptidomimetic inhibitors, including a lead compound with promising bioavailability, safety, and antiviral activity.
All compound designs from the project have been shared openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery.
Reference: “Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors” by Melissa L. Boby, Daren Fearon, Matteo Ferla, Mihajlo Filep, Lizbé Koekemoer, Matthew C. Robinson, The COVID Moonshot Consortium‡, John D. Chodera, Alpha A. Lee, Nir London, Annette von Delft, Frank von Delft, Hagit Achdout, Anthony Aimon, Dominic S. Alonzi, Robert Arbon, Jasmin C. Aschenbrenner, Blake H. Balcomb, Elad Bar-David, Haim Barr, Amir Ben-Shmuel, James Bennett, Vitaliy A. Bilenko, Bruce Borden, Pascale Boulet, Gregory R. Bowman, Lennart Brewitz, Juliane Brun, Sarma BVNBS, Mark Calmiano, Anna Carbery, Daniel W. Carney, Emma Cattermole, Edcon Chang, Eugene Chernyshenko, Austin Clyde, Joseph E. Coffland, Galit Cohen, Jason C. Cole, Alessandro Contini, Lisa Cox, Tristan Ian Croll, Milan Cvitkovic, Steven De Jonghe, Alex Dias, Kim Donckers, David L. Dotson, Alice Douangamath, Shirly Duberstein, Tim Dudgeon, Louise E. Dunnett, Peter Eastman, Noam Erez, Charles J. Eyermann, Michael Fairhead, Gwen Fate, Oleg Fedorov, Rafaela S. Fernandes, Lori Ferrins, Richard Foster, Holly Foster, Laurent Fraisse, Ronen Gabizon, Adolfo García-Sastre, Victor O. Gawriljuk, Paul Gehrtz, Carina Gileadi, Charline Giroud, William G. Glass, Robert C. Glen, Itai Glinert, Andre S. Godoy, Marian Gorichko, Tyler Gorrie-Stone, Ed J. Griffen, Amna Haneef, Storm Hassell Hart, Jag Heer, Michael Henry, Michelle Hill, Sam Horrell, Qiu Yu Judy Huang, Victor D. Huliak, Matthew F. D. Hurley, Tomer Israely, Andrew Jajack, Jitske Jansen, Eric Jnoff, Dirk Jochmans, Tobias John, Benjamin Kaminow, Lulu Kang, Anastassia L. Kantsadi, Peter W. Kenny, J. L. Kiappes, Serhii O. Kinakh, Boris Kovar, Tobias Krojer, Van Ngoc Thuy La, Sophie Laghnimi-Hahn, Bruce A. Lefker, Haim Levy, Ryan M. Lithgo, Ivan G. Logvinenko, Petra Lukacik, Hannah Bruce Macdonald, Elizabeth M. MacLean, Laetitia L. Makower, Tika R. Malla, Peter G. Marples, Tatiana Matviiuk, Willam McCorkindale, Briana L. McGovern, Sharon Melamed, Kostiantyn P. Melnykov, Oleg Michurin, Pascal Miesen, Halina Mikolajek, Bruce F. Milne, David Minh, Aaron Morris, Garrett M. Morris, Melody Jane Morwitzer, Demetri Moustakas, Charles E. Mowbray, Aline M. Nakamura, Jose Brandao Neto, Johan Neyts, Luong Nguyen, Gabriela D. Noske, Vladas Oleinikovas, Glaucius Oliva, Gijs J. Overheul, C. David Owen, Ruby Pai, Jin Pan, Nir Paran, Alexander Matthew Payne, Benjamin Perry, Maneesh Pingle, Jakir Pinjari, Boaz Politi, Ailsa Powell, Vladimír Pšenák, Iván Pulido, Reut Puni, Victor L. Rangel, Rambabu N. Reddi, Paul Rees, St Patrick Reid, Lauren Reid, Efrat Resnick, Emily Grace Ripka, Ralph P. Robinson, Jaime Rodriguez-Guerra, Romel Rosales, Dominic A. Rufa, Kadi Saar, Kumar Singh Saikatendu, Eidarus Salah, David Schaller, Jenke Scheen, Celia A. Schiffer, Christopher J. Schofield, Mikhail Shafeev, Aarif Shaikh, Ala M. Shaqra, Jiye Shi, Khriesto Shurrush, Sukrit Singh, Assa Sittner, Peter Sjö, Rachael Skyner, Adam Smalley, Bart Smeets, Mihaela D. Smilova, Leonardo J. Solmesky, John Spencer, Claire Strain-Damerell, Vishwanath Swamy, Hadas Tamir, Jenny C. Taylor, Rachael E. Tennant, Warren Thompson, Andrew Thompson, Susana Tomásio, Charles W. E. Tomlinson, Igor S. Tsurupa, Anthony Tumber, Ioannis Vakonakis, Ronald P. van Rij, Laura Vangeel, Finny S. Varghese, Mariana Vaschetto, Einat B. Vitner, Vincent Voelz, Andrea Volkamer, Martin A. Walsh, Walter Ward, Charlie Weatherall, Shay Weiss, Kris M. White, Conor Francis Wild, Karolina D. Witt, Matthew Wittmann, Nathan Wright, Yfat Yahalom-Ronen, Nese Kurt Yilmaz, Daniel Zaidmann, Ivy Zhang, Hadeer Zidane, Nicole Zitzmann and Sarah N. Zvornicanin, 10 November 2023, Science.
DOI: 10.1126/science.abo7201
![](https://www.nanoappsmedical.com/wp-content/uploads/2017/05/spacer.jpg)
News
The Silent Battle Within: How Your Organs Choose Between Mom and Dad’s Genes
Research reveals that selective expression of maternal or paternal X chromosomes varies by organ, driven by cellular competition. A new study published today (July 26) in Nature Genetics by the Lymphoid Development Group at the MRC [...]
Study identifies genes increasing risk of severe COVID-19
Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in [...]
Small regions of the brain can take micro-naps while the rest of the brain is awake and vice versa
Sleep and wake: They're totally distinct states of being that define the boundaries of our daily lives. For years, scientists have measured the difference between these instinctual brain processes by observing brain waves, with [...]
Redefining Consciousness: Small Regions of the Brain Can Take Micro-Naps While the Rest of the Brain Is Awake
The study broadly reveals how fast brain waves, previously overlooked, establish fundamental patterns of sleep and wakefulness. Scientists have developed a new method to analyze sleep and wake states by detecting ultra-fast neuronal activity [...]
AI Reveals Health Secrets Through Facial Temperature Mapping
Researchers have found that different facial temperatures correlate with chronic illnesses like diabetes and high blood pressure, and these can be detected using AI with thermal cameras. They highlight the potential of this technology [...]
Breakthrough in aging research: Blocking IL-11 extends lifespan and improves health in mice
In a recent study published in the journal Nature, a team of researchers used murine models and various pharmacological and genetic approaches to examine whether pro-inflammatory signaling involving interleukin (IL)-11, which activates signaling molecules such [...]
Promise for a universal influenza vaccine: Scientists validate theory using 1918 flu virus
New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine—a so-called "one and done" vaccine that confers lifetime immunity against an evolving virus. The study, [...]
New Projects Aim To Pioneer the Future of Neuroscience
One study will investigate the alterations in brain activity at the cellular level caused by psilocybin, the psychoactive substance found in “magic mushrooms.” How do neurons respond to the effects of magic mushrooms? What [...]
Decoding the Decline: Scientific Insights Into Long COVID’s Retreat
Research indicates a significant reduction in long COVID risk, largely due to vaccination and the virus’s evolution. The study analyzes data from over 441,000 veterans, showing lower rates of long COVID among vaccinated individuals compared [...]
Silicon Transformed: A Breakthrough in Laser Nanofabrication
A new method enables precise nanofabrication inside silicon using spatial light modulation and laser pulses, creating advanced nanostructures for potential use in electronics and photonics. Silicon, the cornerstone of modern electronics, photovoltaics, and photonics, [...]
Caught in the actinium: New research could help design better cancer treatments
The element actinium was first discovered at the turn of the 20th century, but even now, nearly 125 years later, researchers still don't have a good grasp on the metal's chemistry. That's because actinium [...]
Innovative Light-Controlled Drugs Could Revolutionize Neuropathic Pain Treatment
A team of researchers from the Institute for Bioengineering of Catalonia (IBEC) has developed light-activated derivatives of the anti-epileptic drug carbamazepine to treat neuropathic pain. Light can be harnessed to target drugs to specific [...]
Green Gold: Turning E-Waste Into a Treasure Trove of Rare Earth Metals
Scientists are developing a process inspired by nature that efficiently recovers europium from old fluorescent lamps. The approach could lead to the long-awaited recycling of rare earth metals. A small molecule that naturally serves [...]
Cambridge Study: AI Chatbots Have an “Empathy Gap,” and It Could Be Dangerous
A new study suggests a framework for “Child Safe AI” in response to recent incidents showing that many children perceive chatbots as quasi-human and reliable. A study has indicated that AI chatbots often exhibit [...]
Nanoparticle-based delivery system could offer treatment for diabetics with rare insulin allergy
Up to 3% of people with diabetes have an allergic reaction to insulin. A team at Forschungszentrum Jülich has now studied a method that could be used to deliver the active substance into the [...]
Nanorobot kills cancer cells in mice with hidden weapon
Researchers at Karolinska Institutet in Sweden have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is exposed only in the tumor microenvironment, sparing healthy cells. [...]