When the coronavirus pandemic broke out, there were hardly any antivirals available. Pharmaceutical companies had developed drugs to combat 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. Because: the development of therapies against diseases that do not pose an immediate threat is not lucrative.
But what if we took advantage of this equation and turned drug development into a collaborative process? Away from the competition. That was the idea behind the “COVID Moonshot,” an open science initiative to develop antivirals against the coronavirus, which launched in March 2020 with a call on Twitter for COVID drug development began. “Calling all medicinal chemists!” wrote Nir London, an engineer at the Weizmann Institute of Science who works in drug research.
Last week, the researchers behind the project published initial results in the journal Science. The project, which involved more than 200 volunteer researchers from 25 countries, found 18,000 drug ideas, leading to the synthesis of 2,400 potential drugs. One of the winners formed the basis of today’s project’s lead candidate: 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 open source project’s initial findings may not seem like much of a “win.” Furthermore, even if the active ingredient works, it will probably still take many years to turn it into a finished therapeutic agent. “But compared to most other drug developments, it’s still been remarkably rapid,” says Charles Mowbray, head of research at the rare disease nonprofit Drugs for Neglected Diseases Initiative (DNDI), a key player. by Moonshot.
Virus without treatment
Although the development of a new drug no longer seems as urgent now, in the last days of the pandemic, as before, the need for another antiviral is very present. Because the next outbreak or the next variant of the virus will surely come. The US National Institute of Allergy and Infectious Diseases has identified ten virus families 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 called peribunyaviruses.
While there are antiviral medications for smallpox and now coronavirus, for many of these families we don’t have any treatment, whether it’s a pill, antibody treatment or anything else. This could be a problem that open source drug development could solve.
There is another potential benefit of the open source model in the pharmaceutical industry: it offers global access. Most current COVID-19 therapies are protected by patents and unaffordable for much of the world. Even in the United States, medicines 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, to $1,390 per dose, when the company sells the drug on the commercial market starting in 2024.
Since the COVID Moonshot project develops drugs that are not protected by patents, they will be processed directly into generics. “The drug can be produced by more than one manufacturer and can be distributed to everyone who needs it, when necessary,” says DNDI’s Mowbray. Slow and often problematic license negotiations with commercial companies are eliminated.
The pharmaceutical industry alone is not enough
Whats Next? DNDI will take the lead in developing the lead candidate, called DNDI-6501, and guide it through preclinical development. And the COVID Moonshot team will also continue their work. Last year, the U.S. National Institutes of Health awarded the consortium nearly $69 million in funding to continue developing oral antivirals. Medicines will be developed not only against coronavirus, but also against West Nile, Zika, dengue and enteroviruses.
However, no drug has come to market through a completely open source process. However, that 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 assumed, openness is not a barrier,” says Matthew Todd, a chemist at University College London and founder of Open Source Pharma. Functional active ingredients can be implemented directly or through the pharmaceutical industry.
Mowbray would like to see greater collaboration in drug research. We don’t know which virus will trigger the next pandemic. Will it be a variant of something we’ve seen before 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 ideas with each other, we probably have a much 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 a review of drug development. We also need to improve our early warning systems. In 2021, the US Centers for Disease Control and Prevention (CDC) launched a surveillance project at some 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, additional testing will only take place 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. As part of 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 departure point can give us information about 200 to 300 people who were on that plane,” CDC program director Cindy Friedman 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.