In a remarkable achievement, the COVID Moonshot Consortium has unveiled a groundbreaking discovery of a fresh class of inhibitors targeting the primary protease of the SARS-CoV-2 virus. This collaborative effort on a global scale has yielded a promising lead compound and, significantly, made thousands of compound designs openly accessible, signifying a significant leap forward in the development of drugs for combating coronavirus infections.
The pioneering research conducted by the COVID Moonshot Consortium introduces a novel category of nonpeptidic inhibitors designed for SARS-CoV-2, highlighting the power of worldwide cooperation and open science in advancing treatments for coronavirus-related illnesses.
Despite its work being accessible to the public since its inception in March 2020, the COVID Moonshot Consortium has now officially published its findings. This open-science, crowdsourced, and patent-free initiative aimed at discovering drugs to combat the SARS-CoV-2 virus has provided a wealth of knowledge concerning the virus’s main protease. These insights have the potential to pave the way for the development of more effective therapeutics, even though the lead therapeutics mentioned by the researchers may not be timely enough to impact the current pandemic, given the stringent timelines and regulatory hurdles associated with drug approval, as noted by Brian Shoichet and Charles Craik in a related Perspective.
Global Collaboration and Progress in Drug Discovery
This novel collaboration brought together over 200 volunteer scientists from 47 academic and industrial institutions spanning 25 countries. Melissa and her colleagues emphasize that the COVID Moonshot represents an exemplar of open science drug discovery, resulting in advancements in the realm of infectious diseases drug development. This is a field of research of paramount public importance but has historically suffered from insufficient funding from the private sector.
Considering its pivotal role in viral replication, the SARS-CoV-2 main protease (Mpro) stands as an appealing target for antiviral drug development. While existing SARS-CoV-2 Mpro inhibitor drugs, such as those derived from preexisting antiviral pipelines like Paxlovid and Xocova, have exhibited clinical success, their utilization has remained relatively limited. Moreover, their peptidomimetic and covalent structures pose challenges in terms of synthesis and administration.
Innovative Drug Design and the Influence of Open Science
In this context, Boby et al. have documented the discovery of an innovative, noncovalent, and nonpeptidic inhibitor scaffold that differs chemically from current Mpro inhibitors. Leveraging a crowdsourcing approach and the collective expertise of hundreds of contributors worldwide, Boby and his team detail their open-science initiative for drug discovery. This effort encompassed machine learning, molecular simulations, and high-throughput structural biology and chemistry to assemble an intricate structural roadmap of the SARS-CoV-2 main protease and its biochemical functions.
From the vast pool of more than 18,000 compound designs generated by the COVID Moonshot Consortium, the researchers pinpointed several noncovalent, nonpeptidomimetic inhibitors, including a lead compound exhibiting promising attributes in terms of bioavailability, safety, and antiviral efficacy.
Notably, all the compound designs stemming from this project have been made publicly available, establishing a comprehensive, open, and intellectual property-free knowledge repository for future endeavors in developing antiviral drugs against coronaviruses.
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, Rambab
Table of Contents
Frequently Asked Questions (FAQs) about Antiviral Discovery
What is the COVID Moonshot Consortium’s recent discovery?
The COVID Moonshot Consortium has made a groundbreaking discovery of a new class of inhibitors targeting the main protease of the SARS-CoV-2 virus, a crucial step in the development of antiviral drugs.
How did the COVID Moonshot Consortium achieve this discovery?
The Consortium achieved this discovery through a global collaboration involving over 200 volunteer scientists from academic and industrial organizations in 25 countries. They utilized open science principles, employing machine learning, molecular simulations, and high-throughput structural biology to map the virus’s main protease and identify potential inhibitors.
What sets this discovery apart from existing treatments?
This discovery introduces noncovalent and nonpeptidic inhibitors, chemically distinct from current ones, offering potential advantages in terms of safety and bioavailability. It opens new avenues for more effective antiviral drug development.
Is the lead compound ready for immediate use against COVID-19?
The lead therapeutics may not be ready to impact the current pandemic due to the challenges of drug approval timelines. However, the techniques and compounds identified hold promise for future antiviral drug development.
How has the COVID Moonshot Consortium contributed to open science?
The Consortium has shared thousands of compound designs openly, creating an intellectual property-free knowledge base for future research on coronavirus drug discovery. This exemplifies the power of open science in advancing public health initiatives.
More about Antiviral Discovery
- Science Article: “Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors”
- COVID Moonshot Consortium
- Paxlovid
- Xocova
4 comments
so, new drug for virus, but not ready for pandemic now? too bad, we need help now. but good for future, i guess.
wow, this covid thing is going crazy! they found some new stuff for the virus. very important, need to find cure!
great! this discovery shows power of teamwork. scientists all over world working together to beat virus. hope more good news soon!
open science is da bomb! sharing info like this helps everyone. let’s fight the virus together! #Teamwork