When the coronavirus pandemic broke out, there were almost no antivirals available. Pharmaceutical companies had developed drugs to fight the flu and a handful of chronic infections. But for a long time they didn’t have much incentive to develop drugs against other viruses that had the potential to cause a pandemic. Why: Developing therapies against diseases that pose no immediate threat is not profitable.
But what if we took advantage of this equation and made drug development a collaborative process? Far from the competition. This was the idea behind the “COVID Moonshot”, an open science initiative to develop antivirals against the coronavirus, launched in March 2020 with an appeal on Twitter Development of anti-COVID drugs started. “An appeal to all medicinal chemists!” wrote Nir London, an engineer at the Weizmann Institute of Science who works in drug research himself.
Last week, the researchers behind the project published their first results in the journal Science. The project, which involved more than 200 volunteer researchers from 25 countries, identified 18,000 pharmaceutical ideas, leading to the synthesis of 2,400 potential drugs. One of the winners formed the basis for today’s lead candidate in the project: a compound that targets the main viral enzyme of the coronavirus. The enzyme, known as Mpro, cuts long viral proteins into short pieces, an important step in viral replication. The active ingredient prevents this enzyme from working. Paxlovid, an antiviral developed by Pfizer after the outbreak of the pandemic, takes a similar approach.
The initial results of the open source project may not seem like a big “win.” Furthermore, even if the active ingredient works, it will likely take many more years to develop it into a finished therapeutic agent. “But if you compare it to most other pharmaceutical developments, it was still extraordinarily fast,” says Charles Mowbray, head of research at the rare disease nonprofit Drugs for Neglected Diseases Initiative (DNDI), one of key Moonshot participants.
Virus without cure
Although the development of a new drug no longer seems as urgent now, in the final days of the pandemic, as it once was, the need for another antiviral is very present. Because the next epidemic or the next variant of the virus will definitely come. The US National Institute of Allergy and Infectious Diseases has identified ten families of viruses that have the potential to become a pandemic. Some of these families contain viruses that many people have heard of: Ebola, West Nile, measles, hepatitis A. Other viruses are little known. These include La Crosse, Oropouche, and Cache Valley, all so-called peribunyaviruses.
While there are antiviral drugs for smallpox and now coronavirus, for many of these families we have no treatment, whether pills, antibodies, or anything else. This may be a problem that open source drug development could solve.
There is another potential advantage of the open source model in the pharmaceutical industry: it offers global access. Most current COVID-19 therapies are protected by patents and are unaffordable for much of the world. Even in the USA drugs are very expensive. When Paxlovid was introduced in 2021, the United States purchased more than 20 million treatment units for $529 each and made them available to the population for free. However, Pfizer says the price will more than double, reaching $1,390 per dose, when the company sells the drug on the commercial market starting in 2024.
As the COVID Moonshot project develops drugs that are not protected by patents, they will be made directly into generic drugs. “The drug can be made by more than one manufacturer, it can be distributed to anyone who needs it, when needed,” says the DNDI’s Mowbray. Slow and often problematic licensing negotiations with commercial companies are eliminated.
The pharmaceutical industry alone is not enough
What’s next? DNDI will take the lead in developing the lead candidate, designated DNDI-6501, and guide it through preclinical development. And the COVID Moonshot team will also continue its work. Last year, the US National Institutes of Health awarded the consortium nearly $69 million in funding to continue developing oral antivirals. Drugs will be developed not only against coronavirus, but also against West Nile, Zika, dengue and enteroviruses.
However, no drug has ever come to market through a completely open source process. However, this does not mean that this model cannot be useful in drug development. Pharmaceutical company Shionogi used data from the COVID Moonshot project to develop its antiviral therapeutic enzitrelvir, which is already approved for emergency use in Japan.
“Contrary to what is often thought, openness is not a barrier,” says Matthew Todd, a chemist at University College London and founder of Open Source Pharma. Working active ingredients can be implemented directly or through the pharmaceutical industry.
Mowbray would like to see more collaboration in drug research. We don’t know which virus will trigger the next pandemic. Will it be a variant of something we’ve already seen or a completely new virus? The idea that a single company could produce enough antiviral drugs to cover such risks seems unrealistic, he says. “If we are willing to share our knowledge with each other, we will probably have a better chance of having the right drug candidates available.”
Early warning and surveillance systems at airports
Preparing for the next pandemic requires more than just reviewing drug development. We also need to improve our early warning systems. In 2021, the Centers for Disease Control and Prevention (CDC) in the United States launched a surveillance project at a handful of major airports to detect emerging variants of SARS-CoV-2.
The agency now plans to expand this program to include 30 new pathogens, including influenza and RSV. For now, the additional testing will only be conducted at four airports: San Francisco International, New York JFK, Logan in Boston and Dulles in Washington.
Here’s how it will be implemented: International travelers flying into an airport where the surveillance program is implemented can voluntarily provide nasal swab samples. These samples are sent to a laboratory for PCR testing. Positive samples will undergo whole genome sequencing. Under the program, wastewater samples are also taken from individual aircraft, as well as from the wastewater system through which all aircraft wastewater passes.
“A sample from a plane from a distant starting point can give us information about 200 to 300 people who were on that plane,” Cindy Friedman, who hosts the CDC program, told US broadcaster CNN. As of October, it had already been used by more than 370,000 travelers from more than 135 countries. 14,000 samples were sequenced.