Interview with Martijn van Hemert, Associate professor and Principal Investigator in molecular virology and antiviral strategies at the Leiden University Medical Center. In recent years, his group has mainly been studying the Chikungunya and Zika viruses, but in the past he has also studied SARS-CoV. Since February 2020, he has shifted his focus to research SARS-CoV-2.
Remdesivir is an antiviral. Can you explain what they are, and what their importance is?
The general public might by now have the idea that vaccines are the magic bullet to solve the COVID-19 crisis. Antivirals are a different way of tackling a viral infection. Instead of stimulating the body to mount an immune response (antibodies) against a virus, like a vaccine does, antivirals are small molecules that will directly inhibit the replication of a virus. These molecules do that by either targeting the virus directly (e.g. by inhibiting viral enzymes like polymerase or protease), by inhibiting host factors that are crucial for virus replication, or by stimulating host factors with an antiviral effect.
We are constantly reminded that a solution for COVID-19 will come from a vaccine rather than anything else…
I think there is too much focus on vaccines. The need for antivirals should be emphasised more, since they have several advantages. Ideally antivirals should be active against a broad spectrum of viruses, not only against SARS-CoV-2, so also against other coronaviruses. They would then provide a cure for current COVID-19 patients, and would also prepare us for outbreaks of new coronaviruses (that might ‘jump’ from animals to humans), which will undoubtedly occur in the future.
And how can we obtain that type of broad-spectrum drugs?
For several viruses, like HIV and hepatitis C virus (HCV), good antivirals have been developed, so it should be possible to develop broadly active drugs against ‘conserved functions’ of these viruses, like the polymerase protein. In that aspect antivirals differ from vaccines, which are very specific and require the host to develop immunity, and therefore will probably not protect against a newly emerging coronavirus that will ‘look slightly different’ from SARS-CoV-2.
Well-developed broad-spectrum coronavirus antivirals have a much greater potential to be useful during future outbreaks, and of course to cure COVID-19 patients. Antivirals might still be required even when vaccines are available, as it is still unclear how effective vaccines are, and how long immunity will last. Also, for certain groups of people, vaccines are not an option.
Another reason is production and distribution. You’ll use antivirals in a fraction of the population, just those who are infected, and perhaps a few more if it’s used in a prophylactic setting to curb (local) outbreaks. On the other hand, you need to vaccinate a large part of the population to prevent the disease. This comes with all kinds of logistical challenges, and even in this pandemic there are unfortunately still large groups of people that will not receive a vaccine.
So in short, we need good vaccines to prevent the infection and protect the population, but we also need to develop good antivirals. We need both.
Coronavirus is very much in the spotlight right now. Yet the existence of different kinds of coronavirus has been known by scientists for many years. How difficult has it been to study them, and create a wide range of drugs and vaccines against these viruses?
For so-called RNA viruses, coronaviruses have very large genomes and a relatively complicated replication cycle, and SARS-CoV-2 is a class 3 pathogen, and therefore you have to study it in special high containment labs (BSL-3 labs). In a scale of 0-4, group 3 biological agent is an agent that can cause severe disease in humans; effective prophylactic or therapeutic measures are usually available.
This requires highly trained skilled personnel. These are difficult aspects, but I do not think there are reasons why it would be more difficult to develop vaccines or antivirals against SARS-CoV2 than for other viruses. I think the number of vaccine development attempts that are ongoing demonstrate this point.
Together with many other colleagues, we have warned for many years of the potential consequences of outbreaks of emerging viruses, and we indicated many times that we should be better prepared, e.g. by developing antivirals against a variety of viruses with a high epidemic potential or otherwise able to cause serious problems.
You are not alone in this quest against coronaviruses, right?
Coronaviruses have been studied by a small community of researchers for many years. Professor Eric Snijder, a well-known expert in the field, has already been studying them for decades.
The development of antivirals is a multi-disciplinary effort that requires scientists from many disciplines ranging from virologists, to biochemists, structural biologists, medicinal chemists etc., etc. For example we are in the IMI-funded CARE project (Corona Accelerated R&D in Europe) and are coordinating the EU-funded H2020 project SCORE (Swift Coronavirus Therapeutics Response). These are very important projects for the development of antiviral drugs against SARS-CoV2 and other coronaviruses.
We’ve seen the incredible development in research and clinical trial processes in the last six months. Everyone from the public and private spheres has moved at an incredible pace to find a solution to this crisis. Did you imagine seeing that level of collaboration and economic power dedicated to this endeavour?
No, I never imagined that, but I think we could have used resources more wisely by investing in research and preparedness in ‘peace time’. I am not only talking about spending money more efficiently , but also about the fact that this extreme crisis response takes a huge toll on many researchers. Over the past half year, many of us have been working 10 to 16 hours a day, and this is not sustainable much longer. Unlike before, we are now also confronted with shortages (or long delivery times) of materials that we need for our research because of the higher demand. I also hope that policy-makers will understand that we need to invest in research and preparedness, so we do not have to depend on such an ‘extreme crisis response’ again in the future.
There are certainly more possibilities for coronavirus research now than ever before, and certain things suddenly go more quickly, but a much earlier and more structured response might have prevented the pandemic getting out of hand as much as it has now.