SARS-CoV-2 pandemic and drug development against COVID-19

Translational Medicine / March 25, 2020

How can Fraunhofer contribute to the fight against the virus? Interview concerning the SARS-CoV-2 pandemic with Prof. Dr. Gerd Geißlinger, Executive Director of the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and Medical Research Officer of the Fraunhofer-Gesellschaft, in an interview for the "Quersumme" (employee magazine of the Fraunhofer-Gesellschaft).

 

Prof. Geißlinger, what do we know about this latest virus and what distinguishes it from earlier types of coronavirus?

We’ve known about coronaviruses in human medicine for quite some time now. We estimate that coronaviruses are responsible for between 10 and 30 percent of all adult respiratory diseases. Most of these, however, are relatively easy to control. The SARS virus, which appeared overnight in 2002, was much more dangerous, as it can lead to acute lung failure. The same was true of the MERS virus in 2012. In genetic terms, the SARS-CoV-2 virus, which causes the disease COVID-19, is around 80 percent identical to the first of these. However, it probably uses additional portals of entry into human cells and also differs in certain parts of its envelope protein.

In what way does this pandemic differ from earlier pandemics such as MERS und SARS?

First and foremost, the rate at which it has snowballed. The world economy is now much more tightly interconnected than it was 10 or 20 years ago. China’s share, in particular, has mushroomed. But the reason SARS-CoV-2 has been able to spread from China so unbelievably quickly is also due to the fact that it is more infectious than SARS. This is because it already starts to multiply in the pharynx and is easily transmitted via droplet infection. Although the relative mortality of COVID-19 is lower than that of SARS, the exponential spread of SARS-CoV-2 means that the number of deaths cannot yet be predicted.

When might we reach a peak in Germany?

If only we knew! No one can say with any certainty right now. It will very much depend on whether people are sensible enough to take the pandemic seriously and alter their behaviour so that the virus is unable to spread as quickly as before. We can only hope that the joint measures taken by federal and state governments will soon take effect. The aim of these measures is, of course, to slow the spread of the virus so that our health care system isn’t swamped.

In your opinion, which are the three most important measures to contain the pandemic?

Firstly, the most important thing at the moment is that we adhere to the social distancing rules, in other words, keep our distance and avoid meeting up with other people. Those who can stay at home should stay at home and, if possible, work from there. Secondly, everyone should continue to observe strict hygiene measures such as frequent handwashing. Thirdly, it is important that those infected be identified as soon as possible and then isolated. This is why it is important that we substantially increase the number of people tested. It’s highly commendable that a number of Fraunhofer Institutes have stepped in to work with university laboratories on this. By the way, any updates to the required measures are being published on the Fraunhofer intranet.

What are the biggest challenges in developing a drug to treat COVID-19? And is there anything that already exists and might be put to good use?

All drug development begins with a search for a suitable point of attack and for a molecule that is able to modify this target. In the case of SARS-CoV-2, this search is made easier by the fact that the virus has already been relatively well characterized. For example, we already know quite a bit about how the virus enters the host cell. Generally speaking, the development of antivirals has been relatively successful in recent years. Look at the treatment of hepatitis C or AIDS, for example, although obviously we’re talking about a different kind of virus here. However, different viruses do display certain similarities in terms of how they multiply and form a new virus particle. In particular, researchers hope that remdesivir, a drug originally developed to combat Ebola, might help here. It is known to inhibit virus replication and is already undergoing clinical trials at several German centers.

There’s talk of shortening the otherwise lengthy process of drug development in acute situations like this. How do we then deal with the resulting risk and possible side effects?

Every new active ingredient has to be safe, well tolerated and carefully tested before being approved for use as a drug. Even in a situation as acute as the current SARS-CoV-2 pandemic, that doesn’t change. However, in the light of the current threat, regulatory authorities have signalled their willingness, where possible, to support and prioritize the approval process. A shorter alternative is to repurpose existing drugs. This is when drugs that have already been approved for other indications are tested to see whether they might also be used against COVID-19. In this case, the drug’s side-effects and safety profile are already known. Therefore, once its efficacy against COVID-19 has been demonstrated, it can be approved relatively quickly for treatment of this new disease. Several Fraunhofer Institutes are particularlyactive in the field of drug repurposing.

What research approaches – or even projects – are being pursued in these life sciences institutes?

One of our traditional research approaches is to take drugs that are already available in clinical practice and test them for use against new indications. That’s what I referred to as drug repurposing. It’s been a specialist area of research of ours for quite some time now and we’re currently applying it to COVID-19. Any promising findings will be followed up by a proof-of-concept initiative. In addition, several institutes are actively involved in attempts to develop a vaccine. And other life science institutes are working – also in cooperation with additional Fraunhofer Groups – on the development of a rapid diagnostic test. The crucial aspect here is that support is being provided by Fraunhofer Institutes working in artificial intelligence and big data. In both drug development and diagnostics research, huge volumes of data have to be sorted and understood. At Fraunhofer, this all comes together in what we call our 4D concept: drugs, diagnostics, devices, data.

And what is your institute, Fraunhofer IME, currently working on?

Fraunhofer IME plays a key role in Exscalate4CoV (E4C), a European consortium funded by the EU. Here, virologists are investigating which proteins are essential for the propagation of SARS-CoV-2. Using an ultrafast virtual screening procedure, our project partners from the Italian pharma company Dompé farmaceutici are now testing in silico substances which might inhibit or modulate these proteins. Meanwhile, researchers at the Hamburg branch of Fraunhofer IME are using our screening robots and our own unique substance libraries to test these predictions in vitro.

 

Interview: Mandy Bartel