Covid Moonshot’s coronavirus pill
In 2020 – 2021, the Covid-19 crisis spurred remote collaboration in many areas of life science. Individuals forged new bridges across disciplines, geographies and traditional boundaries between research and industry. In an unprecedented effort to develop medicines and vaccines for the disease, scientists across the globe came together in virtual environments.
Many scientists employed remote collaboration tools to develop an antiviral coronavirus pill. “We were soon joined by many people who did the hard work because they felt it was the right thing to do”, say the founders of the Covid Moonshot initiative. This was a crowdsourced project that developed on Twitter in March 2020. Casting aside concerns for money or intellectual property, the collective worked together in an unprecedented quest to battle Covid-19.
“People pulled their weight not for glory or reward, but because there was a job that needed doing, and it was one that they could do.”
The aim was simple. To create an effective pill to treat or prevent Covid-19. The group crowdsourced designs for a compound that could intercept Sars Cov-2 and prevent it from hijacking human cells.
The results are impressive. Having identified several lead molecules through this process, the Covid Moonshot scientists are streamlining a process that normally takes years. The group now plans to advance the drugs to clinical trial in 2022.
The Covid Moonshot antiviral programme
Collaborations between research and industry are often hampered by concerns about intellectual property. Yet Covid Moonshot facilitated innovative cooperation across these sectors. Why? Its crowdsourced participants agreed to work openly without claims to monetise the science. They ordered that ‘contributions would have no strings attached, no intellectual property and no remuneration.’
“Covid-19 may yet succumb to the chemical wisdom of crowds.”
The project brought together more than 150 participants from different backgrounds, ranging from academia and biotechnology to pharmaceuticals. Participants in disparate locations worked together remotely using collaboration tools, including Twitter, Zoom, and informatic platforms, as well as courier companies.
The stimulus for the project came from the fact that the founders’ first research grant proposal was rejected by international funders. This, they say, was because funders judged that antiviral medication would take several years to develop.
Instead, money was invested in medical treatments that could be developed quickly: repurposed small-molecule drugs and monoclonal antibodies. Antivirals were deprioritised by the scientific community at this time. Therefore, the Covid Moonshot founders had to find an alternative strategy. This led to the birth of the project as an open, spontaneous and remote collaboration online.
Creating coronavirus pills: the early days
"Initially, a few of us, fuelled by the urgency of the moment, acted on a conviction that our various combined technologies would accelerate drug discovery."
In late January 2020, Chinese scientists had published important results regarding the first 3D crystal structures of the SARS-CoV-2 main protease (Mpro), an essential viral enzyme. Over in Oxfordshire, scientists at Diamond Light Source subsequently began working on X-ray crystallography of the enzyme.
This was to determine the 3D structures of its proteins. Diamond then sent Mpro protein to scientists in Rehovot, in Israel, who identified ‘covalent fragments that attach to proteins irreversibly’.
Then, scientists from across different research centres (the Walsh, F.v.D. and N.L. groups) collaborated on an XChem experiment. This helped to advance the drug development. After the data and write-up were published on the Diamond website, they were published on Twitter on March 7th.
Benefits of online collaboration: the tweets
To the group’s surprise, the results went viral on Twitter almost immediately with 1,000 shares in one week. This unexpected publicity led to several offers of support from fellow scientists. These new recruits resonated with the open-source initiative and were keen to help.
The next stage in the process was to design drug-like molecules. The group launched a tweet to crowdsource ideas for compounds, which they would make and test themselves. Participants were asked to submit their compound suggestions (in machine readable format) to a newly built web page for the project. In just two weeks, the crowdsourcing generated more than 4,000 compounds for testing: an amazing feat!
Using remote collaboration tools for drug development
"Tools for online collaboration have reached a critical mass, both general ones (such as Zoom and Google Docs) and those specific to drug discovery […]."
As cited in Nature, Covid Moonshot also found innovative ways to use digital tools such as Folding@home. Also known as ‘the most powerful supercomputer on the planet’, it helped researchers to build models of viral proteins. According to Nature, Folding@Home was able to predict the most suitable binders for nearly 10,000 compounds each week: that’s an impressive 100 times more than had been attempted before.
The group also employed online collaboration tools, such as CDD Vault, an informatics platform built for drug discovery development. This was crucial for enabling the scientists to collaborate on experiments and analyse data together.
“Serendipitously, for the segments of our project that had the most collaborators — such as submitting ideas for molecules — the requested contributions broke into discrete, doable tasks that easily accommodated each contributor’s availability and know-how.”
Image source: PostEra
In June 2020, the Covid Moonshot collective made a key breakthrough. They had found evidence to suggest that certain sets of molecules inhibited an important Covid-19 protein. The researchers describe reaching an impressive milestone in September 2020, with the discovery of a promising chemical series.
They stated that ‘the compounds inhibited enzymes at submicromolar concentrations, and blocked viral activity at single-digit micromolar concentrations.’
Since then, the group has been developing the compound designs even further. It aims to create molecules that can stay in the blood without being toxic. Once the drugs are ready, hopefully after testing next year, they will be easy to synthesise. They could function as pills for:
- hospitalized patients with coronavirus disease;
- those with mild to moderate covid-19 symptoms;
- those with weakened immune systems;
- health-care workers;
- vaccine-hesitant people, or
- vulnerable or at high-risk populations.
Crucially, the researchers also expect the antivirals to be effective at treating vaccine-resistant variants of Covid-19. Although vaccines target the spike protein of the virus capsule, Covid Moonshot’s compounds target a part of the virus machinery that functions inside cells.
In spite of the barriers to scientific partnerships across geographical borders and traditional sectors, it is clear that remote collaborations, and collaboration tools, are extremely important in life science. We need diverse teams to address complex global problems (such as Covid-19) and find innovative solutions. The Covid Moonshot coronavirus pill is just one example of the incredible successes and rewards that can come from an international, open and remote collaboration.
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