When the corona pandemic broke out, there were almost no antivirals available. Pharmaceutical companies have developed medicines to combat the flu and some 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: Developing therapies against diseases that do not pose an immediate threat is not profitable.
But what would happen if we capitalized on this equation and made drug development 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 that launched in March 2020 with a call on Twitter to COVID drug development started. “Calling all medicinal chemists!” wrote Nir London, an engineer at the Weizmann Institute of Science who works on 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 medicines. One of the winners served as the basis for the project’s main candidate: a compound that targets the coronavirus’ main viral enzyme. 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 functioning. Paxlovid, an antiviral developed by Pfizer after the start of the pandemic, takes a similar approach.
The open source project’s initial findings may not seem like a big “win.” Furthermore, even if the active ingredient works, it will likely still take many years to turn it into a finished therapeutic agent. “But if we compare it 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 Moonshot participant. .
Although the development of a new medicine no longer seems so urgent now, in the last days of the pandemic, as has already happened, the need for another antiviral is very current. Because the next outbreak or the next variant of the virus will certainly 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.
Although there are antiviral medications for smallpox and now coronavirus, for many of these families we have no treatment at all, be it pills, antibody treatments 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 therapies against COVID-19 are protected by patents and are inaccessible to much of the world. Even in the USA medicines are very expensive. When Paxlovid was launched in 2021, the US purchased more than 20 million treatment units for US$529 each and made them available to the population free of charge. 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.
As the COVID Moonshot project develops medicines that are not protected by patents, they will be processed directly into generics. “The medicine can be produced by more than one manufacturer, it can be distributed to everyone who needs it, when necessary”, says Mowbray from DNDI. Slow and often problematic license negotiations with commercial companies are eliminated.
The pharmaceutical industry alone is not enough
What is the next? DNDI will take the lead in developing the lead candidate, designated DNDI-6501, and will 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. Medicines will be developed not only against coronavirus, but also against West Nile, Zika, dengue fever and enterovirus.
However, no medicine has reached the 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 Project COVID Moonshot 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 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 seen before or an entirely new virus? The idea that a single company can produce enough antiviral drugs to cover such risks seems unrealistic, he says. “If we are willing to share ideas with each other, we will likely 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 United States Centers for Disease Control and Prevention (CDC) launched a surveillance project at a handful of large 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 be carried out 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 be subjected to complete genome sequencing. As part of the program, wastewater samples are also collected from individual aircraft – as well as from the wastewater system through which all aircraft wastewater passes.
“A sample from a plane coming from a distant departure point can give us information about 200 to 300 people who were on that plane,” Cindy Friedman, who leads the CDC program, told US broadcaster CNN. By October, it had already been used by more than 370,000 travelers from more than 135 countries. 14,000 samples were sequenced.