kb/data/en.wikipedia.org/wiki/COVID_Moonshot-0.md

title	chunk	source	category	tags	date_saved	instance
COVID Moonshot	1/2	https://en.wikipedia.org/wiki/COVID_Moonshot	reference	science, encyclopedia	2026-05-05T03:48:52.653806+00:00	kb-cron

The COVID Moonshot is a collaborative open-science project started in March 2020 with the goal of developing an un-patented oral antiviral drug to treat SARS-CoV-2, the virus causing COVID-19. COVID Moonshot researchers are targeting the proteins needed to form functioning new viral proteins. They are particularly interested in proteases such as 3C-like protease (Mpro), a coronavirus nonstructural protein that mediates the breaking and replication of proteins. COVID Moonshot may be the first open-science community effort for the development of an antiviral drug. Hundreds of scientists around the world, from academic and industrial organizations, have shared their expertise, resources, data, and results to more rapidly identify, screen, and test candidate compounds for the treatment of COVID-19.

== Project history == Development of antiviral drugs is a complicated and time-consuming multistage process. The public sharing of information in the early stages of genome identification and protein structure identification has accelerated the process of searching for COVID-19 treatments and established a basis for the COVID Moonshot initiative.

=== Genome identification === On January 3, 2020, Chinese virologist Yong-Zhen Zhang of Fudan University and the Shanghai Public Health Clinical Center received a test sample from Wuhan, China, where patients had a pneumonia-like illness. By January 5, Zhang and his team had sequenced a virus from the sample and deposited its genome on GenBank, an international research database maintained by the United States National Center for Biotechnology Information. By January 11, 2020, Edward C. Holmes of the University of Sydney had Zhang's permission to publicly release the genome.

=== Protein structures === With that information, structural biologists world-wide began examining its protein structures. Investigators from the Center for Structural Genomics of Infectious Diseases (CSGID) and other groups began working to characterize the 3D structure of the proteins, sharing their results via the Protein Data Bank (PDB).

Scientists were able to identify a key protein in the virus: 3C-like protease (Mpro). Crucial early X-ray crystallography was done by Zihe Rao and Haitao Yang in Shanghai, China. On January 26, 2020, they submitted a structure of Mpro bound to an inhibitor to the Protein Data Bank. It was released as of February 5, 2020. Rao began coordinating with David Stuart and Martin Walsh at Diamond Light Source, the United Kingdom's synchrotron facility. The Diamond group was able to develop and release a high-resolution crystal structure of unbound Mpro. Approaches to accelerating drug development have been suggested, but identification of proteins and drug development commonly take years. It was possible to sequence the virus and characterize key proteins extremely quickly because the new virus was somewhat familiar. It had a 70–80% sequence similarity to the proteins in the SARS-CoV coronavirus that caused the SARS outbreak in 2002. Researchers could therefore build on what was already known about previous coronaviruses.

=== Possible targets === Identifying and recreating viral proteins in the lab is a first step to developing drugs to attack them and vaccines to protect against them. The COVID Moonshot initiative follows an approach to structure-based drug design in which researchers attempt to find a molecule that will bind tightly to a drug target and prevent it from carrying out its normal activities. In the case of SARS-CoV-2, the coronavirus enters the body and then replicates its genomic RNA, building new copies that are incorporated into new, rapidly spreading viral particles. Protease enzymes or proteases are often desirable drug targets, because proteases are important in the formation and spreading of viral particles. Inhibition of viral proteases can inhibit the virus's ability to replicate itself and spread. 3C-like protease (Mpro), a coronavirus nonstructural protein, is one of the main proteins involved in the replication and transcription of SARS-CoV-2. By understanding Mpro's structure and the ways in which it functions, scientists can identify possible candidates to preemptively bind to Mpro and block its activity. Mpro is not the only possible target for drug design, but it is a highly interesting one.

=== Fragment screening === In collaboration with the University of Oxford and the Weizmann Institute of Science in Rehovot, Israel, the facilities at Diamond Light were used to develop fragment screens utilizing crystallography and mass spectrometry. Nir London's laboratory at the Weizmann Institute contributed technology for identifying compounds that bind irreversibly to target proteins. Frank von Delft and the Nuffield Department of Medicine at the University of Oxford provided technology for rapid crystallographic fragment screening. Researchers examined thousands of possible fragments from diverse screening libraries and identified at least 71 possible protein–ligand crystal structures, chemical fragments which might have the potential to bind to Mpro. These results were immediately made available online.

=== Designing candidates === The open release of the data and its announcement on Twitter on March 7, 2020, mark a critical point in the formation of COVID Moonshot. The scientists shared their information and challenged chemists worldwide to use that information to design potential openly available antiviral drug candidates. They expected a couple of hundred submissions. By May 2020 more than 4,600 design submissions for potential inhibitors were received. By January 2021, the number of unique compound designs had risen to 14,000. In response, those involved began to shift from a spontaneous virtual collaboration to a larger and more organized network of partners with specialized skills and well-articulated goals.