Research efforts to develop treatments against Covid-19
Professor Paul Digard, virologist at The Roslin Institute, University of Edinburgh, tells us about potential routes to Covid-19 treatment and the prospect of having to deal with the virus long-term.
How soon do you think a vaccine against Covid-19 will be available?
Do you think an effective antiviral may be found sooner?
Paul Digard: Yes, there are two routes through which we could come up with something relatively quickly: one is looking at compounds that affect the patients’ response rather than the virus directly, like immunomodulators, and the other is looking at antivirals that have been developed against other viruses and that we know are safe to use in people. I wouldn’t be surprised if some of these drugs are already being used in people under emergency-use licences. What is harder to predict is how long it will take to find something that is globally useful and that can be extensively rolled out. There is a chance that we will get antivirals before a vaccine.
What do we know about Covid-19 that will help to develop an effective therapy?
Paul Digard: Although there is still much to learn about the virus’ epidemiological parameters, we know enough about how it replicates to start designing antivirals.
If we are looking to use small molecule inhibitors, do we use one that disrupts the virus or do we try to use ones that disrupt the bad aspects of the body’s response to the virus? Understanding how the virus causes disease, and how that the spectrum of disease varies between different people, such as those with underlying health issues, makes the prediction of therapies that target the host response even more difficult.
Some of the drugs that I know are being looked at attack processes that are common in different types of virus, ‘generics’ if you like. If you think back the AIDS pandemic, the very first antiviral that was used against HIV was an inhibitor of Herpes virus. Like acyclovir, it was a synthetic nucleoside analogue that interferes with viral replication. One of the drugs that is being tried against SARS-Cov-2 is a nucleoside analogue that was developed against an influenza virus. Ribavirin, is another drug of this class that might be generically useful.
Then, there are more specialized drugs that target a feature that is common to certain viruses like SARS, HIV and Hepatitis C. These viruses make their proteins from a large precursor polypeptide that gets cut up into fragments and gives rise to fragments that carry out different functions. Drugs that block the protease steps are very successful for treating HIV and Hepatitis C and are being trialled against SARS-Cov-2 to see if they work. We are not starting from zero when it comes to antivirals against Covid-19.
However, a note of warning, from our experience of working with flu, these agents are better as prophylactics, they are not so good for treating severe illness. With antivirals it is a challenge to get them into the patient soon enough to be useful. When the patient is in respiratory failure and in the intensive care unit, antivirals tend to be too late; by then the damage is coming from the body’s reaction to the infection and not so much from the virus itself.
How do you envisage production of any effective drug will be scaled up to meet demand?
Paul Digard: The pharmaceutical industry has experience of doing this, they managed with HIV 20 years ago. It can cause shortages of precursor chemicals, that was a limiting factor for the production of one of the earlier drugs for HIV. Obviously, if countries are locked down and global trade is hindered, it won’t help.
It is also worth remembering, and this applies to vaccines too, that you don’t need to give it to everybody. If only relatively small amounts are available, targeted use in healthcare and essential services workers would be very helpful at tackling the pandemic.
How could future outbreaks of zoonotic diseases be prevented?
Paul Digard: Lessons should have been learnt already. To stop animal viruses from jumping into humans we need to get rid of wet markets, they are perfect mixing vessels to get viruses into new hosts. Although it is likely that bats serve as reservoir hosts for SARS-Cov-2, the virus is likely to have gone through an intermediate host before infecting humans. Further knowledge about this will help us to understand the risk of future re-emergence events.
What do you think of the EU’s recent research funding announcement to tackle Covid-19?
Paul Digard: The rapid mobilisation of funds is very welcome and the projects selected look sensible. I think it is important to realize that we are unlikely to get rid of the virus quickly, there is a chance that it will come back in the winter. We need both short and long term fixes for this. At this point anything that works to treat the infection is welcome, down the line we should look for something that works really well.
For example, we should be looking at developing a test to predict patients’ response to the virus (what makes them likely to have a good or bad outcome?) and trying to understand what patient responses are associated with a good outcome. This will contribute to the development of therapies that target the host response rather than the virus directly.