Leuven’s non-stop search for a coronavirus drug

Summary

The Rega Institute has completed tests on more than 15,000 compounds and is setting up animal testing to narrow down potential treatments

Screening central

The Rega Institute at KU Leuven hit the headlines last month with the news that 15,000 medicinal compounds were being flown over from the USA for rapid testing against the coronavirus Covid-19.

Being chosen for this task by the Bill & Melinda Gates Foundation was a high-profile endorsement of the Institute’s preparations for the challenge of a virus pandemic. “Our facility has been operational for about two years, and we’ve done a lot of dry runs, but now we are out of peace time and into the war,” says Johan Neyts, professor of virology at KU Leuven, who is leading the work.

The idea is to look through libraries of medicinal compounds to see if there is anything already out there that can help treat people infected with Covid-19. It might be a drug used to treat another condition or a compound under development that could quickly be brought into use if found effective.

First catch your virus

The test is fairly simple. Cells growing in a dish are infected with the virus and start to die. A dose of each candidate drug is then added to see if it slows down or stops the process. A positive result means the molecule is worth further investigation.

Doing this by hand is time-consuming and labour-intensive. Some of the steps can be automated, but generally still need to be overseen by technicians. And if the virus is dangerous, they need wear protective suits and work in rooms with stringent decontamination systems.

So, in 2017 the Rega Institute set out to build a facility where the whole process could be automated and placed inside a sealed room. Screening takes place safely, without exposing technicians to the virus, and can operate 24 hours a day, seven days a week.

Virologist Johan Neyts

Before the machines can be turned on, however, the target virus has to be isolated. In the case of Covid-19, the source was a nose swab taken from the first Belgian patient, someone who brought the virus back from Wuhan but did not fall ill.

This sample was carefully grown in the lab, making sure it was not contaminated with other viruses and that it did not mutate in order to grow more efficiently in its new environment. “You need enough virus to test thousands and thousands of samples but the certainty that it is still the same virus isolated from that patient’s nose,” explains Neyts.

Technicians at the Institute worked around the clock to complete these tests in the early weeks of the outbreak. “We could not afford to lose time, but we could also lose time by beginning too quickly. Everything has to be fine-tuned before you start such a big exercise.”

We need to give the public a realistic view and not announce everything we find in the lab as some kind of breakthrough

- Virologist Johan Neyts

Since then, the facility has been running at full capacity, processing the 15,000 compounds flown over from the USA, together with thousands of other candidates. These come from KU Leuven’s own collections, from other academic institutions and from big pharmaceutical companies.

Although the process is automated, it still makes huge demands on the Rega Institute’s staff. “We’ve had to push the capacity of the facility to its limits,” says Neyts, “such as working on the software to save a minute here or 15 seconds there, so that the volume of tests can be as high as possible.”

While the initial screening is very fast, Neyts is cautious about saying too much about the results. “We need to give the public a realistic view and not announce everything we find in the lab as some kind of breakthrough.”

Cautious optimism

Positive signs need to be checked and re-checked, and then further questions asked about how useful each compound might be as a potential treatment. “This takes a little time, but it is worth doing so that you can select the molecules that you want to test in humans,” he explains. “We should also not overload the hospitals and doctors looking after Covid patients with all kinds of studies that, in the end, may not make sense.”

An important step in this follow-up is the development of an animal model that can be used to test candidate drugs. This is something else the Rega Institute is working on.

The challenge is to find an animal that gets the disease in the same way as humans. “First of all, the virus has to replicate, then the immune system needs to go into overdrive, reacting to the infection as it does in humans.”

That does not happen efficiently in mice, the most common laboratory animal, so alternatives are being explored.

The Rega Institute's automated lab

The most important lesson learned from the outbreak so far is that the researchers were right to prepare in advance. “We are very grateful to the Flemish government and the university in Leuven for funding this facility,” says Neyts. “These were significant investments, and I’m happy they believed our warnings about preparing for a pandemic.”

But there is also frustration that the message was not heard at the global level. With decisive international action and investment after the Sars-1 corona virus outbreak in 2003, Neyts believes we would already have a potent drug to treat any new coronavirus.

“With an investment of just €300-€400 million – the cost of three or four fighter jets – we could have had this protection for human health and the economy.”

Photos: top (c)Anja Symons, above (c)Rob Stevens