This year’s World Lung Day motto is “A Lifetime of Lung Health.” From a scientific perspective, is there an age group whose lung health is particularly at risk from viral infections?

Vulnerability is not limited to a single age group. The highest risk occurs at both ends of of life as well throughout live in certain risk-groups. Respiratory viruses can be a major burden at any age, as we saw with COVID 19 and with frequent RSV hospitalisations in infants. However, the largest at risk population is older adults and people with chronic respiratory conditions. Age related immune changes, comorbidities like COPD and heart disease, and pre existing lung disease all increase the risk of severe outcomes.

So, from a lifelong perspective, protecting lung health is especially important in early childhood, when the lungs are still developing, and in later life, when the body becomes less resilient. However, people with chronic lung diseases like asthma and COPD, or weakened immune systems can be at increased risk at any age.

Within the NoVir project, working with patients with pre-existing conditions such as asthma and COPD plays an important role. In how far do viruses affect these individuals differently than people without such conditions?

People with asthma or COPD already have sensitive, inflamed or damaged airways. A viral infection can add another layer of inflammation, increase mucus production and further narrow the airways. The natural antiviral response of the airways can be impaired in some patients with asthma or COPD due to a dysregulated Interferon Lambda pathway, potentially allowing the virus to multiply more effectively. As a result, an infection that causes only a common cold in an otherwise healthy person may trigger a marked worsening of breathlessness, coughing or wheezing in someone with chronic lung disease. We call this an exacerbation, or flare-up.

These flare-ups may require additional medication, emergency treatment or hospitalisation. In asthma and COPD, repeated exacerbations also contribute to a lasting decline in lung function. With ETH47, we want to restore their natural firewall against viruses to prevent and limit viral infections and subsequent flare-ups.

The antiviral drug ETH47 is currently being tested in clinical trials. It is intended to better protect people with pre-existing conditions against viral infections. What procedures does such a clinical trial involve?

In a previous interview, my colleague Steffen used a very helpful image to explain what it takes to develop a new medicine: he compared the process to testing a new airplane before passengers are allowed to fly on it. Following this metaphor, clinical trials are like test flights, the medicine is tested step by step under carefully controlled conditions. A clinical trial follows a prepared plan, much like a test flight follows a detailed flight plan. The plan describes who may take part, which tests will be performed, how the medicine will be given and how participants’ safety will be monitored. Independent ethics committees and health authorities review and approve it before the trial begins. Potential volunteers first receive clear information about the study and can ask questions. They decide freely whether to participate and provide written consent. Doctors then carry out health checks to confirm that they are suitable for the trial.

During the trial, participants receive the medicine, or, in some trials, a placebo that looks the same but contains no active medicine. Doctors and nurses monitor them closely through regular examinations, blood tests, vital-sign measurements and questions about how they feel. Any unwanted effects are carefully recorded. At the end, researchers compare all the results to determine whether the medicine is sufficiently safe and whether it has the intended effect. Each clinical trial is therefore like another carefully controlled test flight: it provides important information before a medicine can move to the next stage of development.

Which results are particularly important when you analyse the study?

The most important question is always whether ETH47 is safe and well tolerated by the volunteers. We carefully record any side effects and monitor the participants’ health throughout the trial. We then look at whether ETH47 works as intended. ETH47 uses mRNA to give cells in the airways instructions to produce interferon lambda, a natural protein that helps the body fight viral infections. You can think of interferon lambda as an alarm signal: it warns nearby cells and helps put them into an antiviral state, making it more difficult for a virus to multiply and spread.

In the current Phase 2 trial, volunteers with asthma are exposed under carefully controlled conditions to a common cold virus. We compare people who receive ETH47 with those who receive a placebo, which does not contain the active medicine. We ask about symptoms in both the upper airways, such as a blocked or runny nose, and the lower airways, such as coughing, wheezing or shortness of breath. We also take nasal swabs, similar to the COVID-19 tests many people remember from the pandemic, to measure how much virus is present in the nose. Together, these results show us whether participants treated with ETH47 have less virus and milder symptoms than those who received placebo.

What further steps are required before ETH47 can receive marketing authorisation?

Developing a medicine is a step-by-step process, and ETH47 still has several stages to complete. We have already carried out a Phase 1 trial in which healthy volunteers received a single dose. This provided important information about safety and tolerability. We have also completed a Phase 2 trial in volunteers with asthma. The final results are not yet available, however from an analysis that was performed when half of the planned total number of participants were dosed, we know that ETH47 was safe and well tolerated in asthmatics and was very potent in reducing the amount of virus in the nose. The next step is to study repeated use. We plan to test whether giving ETH47 several times, for example, once a week for four weeks, is safe and well tolerated in healthy volunteers. If those results are encouraging, repeated dosing would then also be studied in people with asthma in a Phase 2 trial.

The final clinical stage would be larger Phase 3 trials, potentially involving thousands of people with asthma. These studies would provide further evidence about safety and would test ETH47 under everyday conditions, for example, across the autumn and winter, when respiratory infections are more common. The key question would be whether ETH47 can protect people with asthma or COPD from virus-related flare-ups. If the overall results show that the medicine is effective and safe the full set of data can be submitted to the regulatory authorities. These authorities will then decide whether ETH47 can be approved for use.

To what extent could current research in drug development improve the management of chronic lung diseases in the future?

Current drug research could make a major difference by helping us move from simply treating flare-ups to preventing them. Today, medicines for asthma and COPD can control symptoms and reduce inflammation, but they do not treat the actual cause of those flare ups. Respiratory viruses can still trigger serious worsening of the disease. Future treatments may provide an extra layer of protection by stopping viruses from multiplying or by strengthening the body’s own antiviral defences. They could be used during seasons when respiratory infections are common or when a virus is spreading widely.

If these approaches are successful, people with chronic lung diseases could experience fewer and milder flare-ups, need less emergency treatment and spend less time in hospital. Over the longer term, preventing repeated flare-ups helps to preserve lung function and improve quality of life.

First of all, what exactly happens during zoonotic events, and how do they occur?

The term zoonosis refers to any infectious disease, including viral infections, that is transmitted from non-human animals to humans. We often call this a “host jump” because the virus “jumps” from its original host animal into the human population. These jumps usually occur due to close encounters with the infected animal population – either by direct contact with the animal, for example, with pets or domesticated animals on farms, or indirectly through exposure to animal products such as meat and dairy, or, as in the case of hantaviruses, feces and urine. Most of the time, while these viruses may cause severe disease in infected humans, they cannot be passed on to other humans. Rabies, for example, is contracted by animal bites and is fatal if not treated, but is usually not transmitted human-to-human. In contrast, if a zoonotic virus acquires the ability to transmit from person to person, it can cause larger outbreaks and even pandemics.

Which other human viruses originated through zoonotic transmission, and how can scientists identify the original host?

The majority of human viruses, including those that have caused major epidemics and pandemics, are thought to have jumped into the human population from animals. Influenza viruses spilled over from birds and pigs into the human population. HIV-1, the virus that causes AIDS, jumped over from chimpanzees, and many hemorrhagic fever viruses are transmitted from primates or rodents to humans via insect bites.

Finding the original host is often not trivial and involves a lot of detective work. By comparing how viral genetic sequences change over time and across locations, scientists can estimate when and where a virus is most likely to have jumped into the human population. This is then combined with fieldwork, like testing suspect animal populations or products, to get a sense of where human-animal contact might have occurred. This process can take years, and for some viruses, may never have a final answer. For example, SARS-CoV-2 likely originated in bats, like other human coronaviruses before, but it probably did not jump directly into humans from an infected bat. Instead, there was likely an intermediate host, an animal that became infected and then passed the virus on to humans. We currently do not know for sure which animal served as this intermediate host.

Influenza viruses occur in both humans and animals. What exactly happens inside a virus when it changes its host from animals to humans?

Viruses are usually very well adapted to their original hosts, but some features that enable them to replicate efficiently in one species can make it difficult to infect another. Therefore, viruses must adapt to their new hosts in various ways. For influenza A viruses, we understand some of these adaptations quite well because we can directly compare virus strains from birds and humans. They are related to each other, but only the human ones replicate and spread efficiently in the human population.

For example, to infect cells, bird flu viruses, so-called avian influenza viruses, bind to a sugar molecule called sialic acid in the gastrointestinal tract of birds. Sialic acid is also found in the respiratory tract of humans, but its chemical structure is slightly different. This small difference is enough to prevent infection with bird influenza viruses unless they change their ability to bind to the different sialic acid types. The seasonal flu is caused by influenza strains that bind very effectively to the human version of sialic acid and therefore spread easily between people. This is just one example of many interactions between the virus and the new host that need to be fine-tuned. The totality of all factors that prevent viruses from easily jumping into a new species is called the “species barrier”, and it is the reason that these jumps are, luckily for us, comparatively rare.

Could you explain how the interaction between a virus and its host further transforms when a virus such as the Influenza A virus begins to spread from human to human?

Viruses are so-called “obligate parasites”, which means that they need to infect cells to be able to replicate and spread. They do this by binding to and exploiting the function of cellular molecules. Since those molecules often differ between birds and humans, influenza viruses need to adapt to these changes. For example, the viral protein that multiplies genetic information, called the RNA polymerase, interacts with a cellular protein that enhances its activity. In avian strains, RNA polymerase binds strongly to the avian version of the cellular protein, but not to the human version. One of the most frequently observed mutations in influenza viruses that successfully replicate in humans converts the RNA polymerase into a strong binder of the human protein. Similarly, viruses must find ways to avoid the immune response of the new host. Humans express a protein called MxA that very efficiently counters infection with most avian influenza viruses. In contrast, the human-adapted strain can replicate very efficiently even in the presence of MxA.

How does the human immune system react upon first contact with a virus that previously infected only animals?

Our immune system fights viruses off with two different strategies. The innate immune system is the first line of defense. It does not recognize which virus is present, but simply that there is an “invader” that needs to be eliminated. In contrast, the adaptive immune system fights viruses with strategies tailored to each virus, such as antibodies. This can be incredibly effective but requires that the host has already been infected with this particular virus before or is vaccinated against it. For viruses that enter the human population for the first time, we generally cannot mount an effective adaptive immune response. We have seen this with SARS-CoV-2, which spread easily through the human population because, amongst other things, infected patients were not initially protected by the adaptive immune response. Later on, as many people were either vaccinated or previously infected, infection numbers have declined.

Within NoVir, you are testing the efficacy of ETH47, the antiviral nasal spray, in pre-clinical studies. To what extent could this drug serve as a way to protect people from pandemics caused by respiratory viruses?

ETH47 is not a traditional antiviral, as it does not target a specific viral protein; instead, it boosts the innate immune response. Therefore, it can broadly act against many viruses by strengthening the first line of defense. We envision that in a pandemic scenario, this could help to limit transmission and protect vulnerable populations until more virus-specific measures, such as traditional antivirals and vaccines, are developed.

The COVID-19 pandemic was also most likely triggered by a zoonotic event. What lessons regarding pandemic preparedness have you, as a virologist, drawn from that period? Do these lessons influence your research within NoVir?

To me, the COVID-19 pandemic illustrates perfectly how basic and translational research can complement and elevate each other. I strongly believe that we need both to successfully combat new viruses. Scientists were able to develop diagnostic tests, antivirals, and vaccines at unprecedented speed by building on a vast body of research across many subjects that were often considered a bit niche before the pandemic. Basic research on coronaviruses, even those that “just” cause the common cold, laid the foundation for understanding the molecular biology of this specific coronavirus. Similarly, mRNA vaccines were made possible by years of prior research and technology development.

In NoVir, we combine basic research on how the innate immune system reacts to viral infections and how we can influence that by boosting certain aspects of the innate immune response with very translational aspects, such as our clinical trial in asthma patients. So hopefully, we can deliver both immediate benefits to patients and, at the same time, contribute to our fundamental understanding of the immune system.

You began your academic career in the field of molecular medicine. What fascinated you most about this field?

What fascinated me most about molecular medicine was that it connects the tiniest details of biology to real people’s health. You can look at how a single molecule or a small change in a cell can lead to disease and that understanding can point directly to a solution.

I also loved the feeling that the work is both detective work and teamwork: you ask “how does the disease actually start?” and then use that knowledge to design better ways to prevent or treat illness. That early experience is a big reason why I later focused on immune system and vaccines. Vaccines are one of the most powerful examples of turning basic biology into protection in everyday life.

In what ways are the fields of molecular medicine and virology connected? Could one say that they are complementary to each other?

Molecular medicine and virology are closely connected because they both focus on what happens at a very small scale (inside cells and at the level of genes and proteins). Virology helps us understand how viruses enter cells, hijack the cell’s machinery, and spread. Molecular medicine uses many of the same tools and ways of thinking to understand disease processes and to develop ways to prevent or treat them.

Virology explains the virus side of the story, and molecular medicine helps explain the body’s response and how we can influence that response with treatments or vaccines. When you combine them, you get a much clearer picture of where interventions can work best, from blocking infection early to shaping a strong, lasting immune protection.

In your opinion, what is the main challenge of developing an antiviral that is effective against multiple viral families?

The main challenge is that different viral families can be very different from each other. They don’t all use the same “tools” to copy themselves, and different ways of entering and taking over our cells. So, a drug that works well for one family may simply have nothing to latch onto in another.

To make an antiviral that works broadly, you need to target something that is shared, this could be a host-cell process that viruses commonly exploit or boosting the host immunity. But that comes with a second challenge: you must avoid harming the host’s own cells. So, the balance is finding a target that is common enough to many viruses, but specific and safe enough that you can block infection without causing side effects.

Your team is testing the therapeutic efficiency of ETH47 during viral infection. What will supposedly happen in the body when the drug is used after viral exposure?

After someone has been exposed to a virus, the infection usually starts with a “race” between the virus multiplying and the immune system reacting. ETH47 boosts the immune response to help the body react faster and more effective, so the virus has less time to spread.

Timing matters a lot: used soon after exposure, it may help the immune system get ahead of the virus. Used later, when inflammation is already high, the benefit can be smaller and in some cases, you have to be careful not to push the immune system into an overreaction. That’s why we test not only whether it works, but also when it works best.

ETH47 is also intended as a preventive tool against viral infections. What did you find out so far about the protective effect of the compound?

Previous data showed that ETH47 strengthens the body’s early antiviral defence by priming innate immune responses, helping the immune system react faster and more robustly after exposure to respiratory viruses such as Influenza and SARS-CoV2.

Currently, we are assessing the efficacy against further virus families and delivery routes and in this setting our results suggest that ETH47 can strengthen the body’s early antiviral defence. In our studies, we see signals that it helps the immune system respond faster and stronger after exposure. The rapid response is used to slow viruses down in the first days and milder illness.

What further research activities have you planned within the NoVir project?

We want to test protection against many viruses, to see how broad and robust the effect of ETH47 is across different viral families. We plan to compare and optimize delivery methods in other words, the best way to administer the compound so it provides strong protection and is practical to use for each indication.

In parallel, an important part of our research is to build on our existing understanding of the immune system and deepen the mechanistic picture: which immune cells are doing what, which ones are most important for protection, and how these cells communicate during an infection. This deeper understanding doesn’t just advance the NoVir project, it also provides us with the knowledge needed to design and develop next-generation vaccines and immune-based interventions that can be made available more quickly in the event of a future pandemic.

In your opinion, what is the most important lesson learned from the COVID-19 pandemic regarding pandemic preparedness?

The most critical lesson is that we need to be prepared before a pandemic strikes, not during it. COVID-19 showed us that developing treatments and vaccines from scratch takes precious time that costs lives. Think of it like having a fire extinguisher at home: you don't want to start shopping for one when your kitchen is already on fire. What became clear is that investing in research and having tools at hand in advance makes all the difference. The reason we could develop COVID vaccines so quickly was because scientists had spent decades working on mRNA technology not specifically for COVID, but as a general platform that could be quickly adapted. Without those years of preparation, we would have been in a far worse situation. We also learned that having strong international cooperation and well-funded public health systems isn't a luxury, it's essential. Viruses don't respect borders, so our response can't be limited by them either.

Why is it important to strengthen not only political but also scientific collaboration at the transnational level to counter epidemic threats?

Imagine trying to solve a huge puzzle when everyone working on it only has access to a few pieces and can't share them. That's what happens when countries work in isolation. Viruses spread globally within days, so our scientific response needs to be equally fast and coordinated. Scientific collaboration across borders brings crucial advantages and prevents "reinventing the wheel." If researchers in one country make a discovery, scientists elsewhere can immediately build on that knowledge. During COVID-19, international collaboration allowed vaccine development at unprecedented speed because teams worldwide shared data in real-time. Partners from different countries also bring different strengths. Some have unmatched expertise in certain fields of research, others have well-established hubs for clinical trials, and others world-class infrastructure for manufacturing. By combining these strengths, we can move from laboratory findings to actual treatments much faster than any single country could alone.

"Viruses spread globally within days, so our scientific response needs to be equally fast and coordinated."

How do the NoVir project and specifically your company contribute to improving the response to epidemic threats?

The NoVir project is driving forward the development of ETH47, a treatment that teaches your body's immune system to be ready for unwanted viral visitors before they can cause trouble. What makes ETH47 valuable for pandemic preparedness is that it could work against virus variants we haven't encountered yet. When a new pandemic virus emerges, we wouldn't have to start from zero. With ETH47 available, we'd have an immediate tool to protect people while scientists develop specific vaccines. Ethris initially developed ETH47, and through the NoVir consortium, we're guiding it through clinical trials. Our partners at the Technical University of Munich and Aarhus University conduct additional laboratory studies, gathering evidence about how well ETH47 works against different viruses.

What makes ETH47 stand out compared to other antiviral drugs?

Most vaccines and conventional antiviral medications work like a very specific key that only fits one lock. They can be very effective, but they only work against viruses they were designed for, and viruses can develop resistance by changing their structure. This means that if the virus changes even slightly, the key doesn't work. ETH47 takes a different approach. Instead of targeting the virus, it activates your body's own built-in antiviral defense system. It delivers instructions (in the form of mRNA) that tell cells in your airways to produce interferon lambda – a natural protein your body normally makes when fighting viral infections. Interferon lambda acts like an alarm system, putting cells into an antiviral state so viruses have much harder time infecting them. Because it's part of your body's natural response, it works against many different respiratory viruses. Whether it's a common cold, a flu variant that jumps from animals to humans, or a completely new coronavirus. Another advantage is that ETH47 works locally, right where you apply it in your nose and airways, concentrating effects exactly where needed while causing minimal effects elsewhere. Traditional antiviral pills travel through your entire bloodstream, sometimes causing side effects in organs that aren't even infected. ETH47's room-temperature stability makes it practical for widespread use, unlike treatments requiring complicated cold storage. The ultimate aim is a self-applied, easy to use product that you could keep in a medicine cabinet like a nasal spray.

To what extent could ETH47 be a game changer for future epidemics?

ETH47 has potential to fundamentally change how we protect people during outbreaks. First, it addresses a major gap: the time it takes to develop specific treatments. ETH47 could be deployed immediately when a new respiratory virus emerges because it strengthens the body's natural defenses that work against many different viruses. Second, ETH47 works at the "front door": the nasal passages and airways where respiratory viruses first enter. By stopping them there, it prevents spread deeper into your lungs. This is especially important for people with chronic lung diseases such as asthma and COPD, whose airways are already sensitive and inflamed. Even a common cold virus can cause a serious flare-up, called an exacerbation, that makes breathing much harder and can become life-threatening. Third, ETH47 is already pretty stable: it can sit at room temperature for more than a week, in the fridge for months, and in a normal freezer for years. That’s a big step up from the early COVID vaccines, which had to be kept super cold and were hard to transport. In parallel with the NoVir project, we are working on spray-dried formulations that allow for even longer storage at room temperature. This makes distribution much easier to remote areas without cold-storage infrastructure. During a pandemic, these logistical advantages could save countless lives. Finally, the NoVir team is investigating how ETH47 works together with existing antivirals, potentially making both more effective.

"ETH47 has the potential to fundamentally change how we protect people during pandemic outbreaks"

The NoVir consortium is conducting both clinical and pre-clinical trials. What is the goal of these different types of studies?

Developing a new medicine is like designing and testing a new airplane before passengers fly on it. Pre-clinical and clinical studies are different testing phases that answer different questions. Pre-clinical studies are laboratory testing – like testing airplane parts in a wind tunnel before building the full aircraft. Scientists use cells and animal models to answer fundamental questions: Does the medicine work as we think? At what dose? Are there harmful effects? This is where our partners at the Technical University of Munich and Aarhus University play a crucial role. They're conducting sophisticated laboratory experiments to understand exactly how ETH47 works against different types of viruses in controlled settings. They're also exploring whether ETH47 could work in combination with other treatments and investigating different ways to deliver it beyond nasal spray. Clinical studies test the medicine in actual human volunteers, like test flights to keep the airplane picture. Phase 1 trials, which ETH47 completed, involve small numbers of healthy volunteers. It focuses on confirming ETH47 is safe and works as expected in people. Phase 2 trials, currently underway at Ethris, test whether the medicine actually helps patients at risk. For ETH47, volunteers with asthma are deliberately exposed to the common cold virus to confirm that ETH47 reduces their symptoms compared to placebo. By combining clinical evidence from real patients with the detailed laboratory insights from our academic partners, we build a complete understanding of how ETH47 can protect people during viral outbreaks.

How has the development of ETH47 advanced, and what challenges remain to be addressed?

ETH47 has made substantial progress. It successfully completed Phase 1 clinical testing, showing it's safe, well-tolerated, and produces interferon lambda in airways as intended. Based on these results, we've now moved into Phase 2 trials where we're testing whether ETH47 actually prevents viral illness in people with asthma who are exposed to rhinovirus. Meanwhile, our consortium partners are advancing the science in parallel. The Technical University of Munich and Aarhus University are conducting laboratory studies that go beyond what we can test clinically right now. They are investigating ETH47’s effectiveness against a broad spectrum of viruses, including respiratory pathogens and viruses transmitted via other routes, exploring its potential to enhance other antiviral treatments in combination settings, and evaluating alternative delivery approaches. This pre-clinical work is essential because it helps us understand ETH47's full potential and prepares us for future clinical trials with different patient groups or virus types. The main challenges ahead involve scaling up our evidence. We need larger Phase 3 trials with thousands of participants to confirm effectiveness across diverse populations before regulatory approval. We also need to determine optimal dosing strategies, i.e. how much, how often, and for how long people should use ETH47 for maximum protection. The NoVir project runs through April 2027, giving us time to complete some of these crucial studies. If everything continues positively, ETH47 could be available within the next few years as a practical tool for pandemic preparedness, backed by both robust clinical evidence and deep scientific understanding of how it works.