Covid-19: Boosting antiviral research

As countries around the world implement national pandemic plans, we take a look at some of the research strategies being pursued to tackle Covid-19.

Funding research and innovation projects to find a cure for Covid-19 is a vital part of the EU plan to tackle the current coronavirus crisis.

On the 30th January the European commission committed €47.5 million to research projects aimed at understanding the novel coronavirus (SARS-CoV-2) and develop new treatments, diagnostic tests and vaccines. At the time of writing 18 projects involving 136 research teams from across the EU and beyond have been shortlisted for funding. The Commission also called for research proposals by the end of March focusing on developing treatments and diagnostics to tackle the current outbreak and increase preparedness for future, within the framework of the Innovative Medicines Initiative and for a €90 million total investment. On 16 March, the Commission provided financial support to the tune of €80 million to CureVac, an innovative vaccine developer in Germany, to support work on the coronavirus vaccine.

EU funding for COVID-19 research

Researchers welcome this rapid mobilisation of funds.

Professor Giovanni Rezza, MD, Director of the Department of Infectious Diseases at the Istituto Superiore di Sanità, Roma, ItalyProfessor Giovanni Rezza, Director of the Department of Infectious Diseases at the Istituto Superiore di Sanità, Rome: “We need these products; the current social distancing measures to contain the virus can be applied for one, maybe two months, but it is difficult to sustain them indefinitely.”

After China, Italy has been one of the worst hit countries. As the number of Covid-19 deaths have increased, more restrictive lockdown measures have had to be introduced to slow down the transmission rate and relieve the pressure on healthcare systems.

There is consensus among researchers that despite the enormous progress towards developing a vaccine it is likely to take between 12 and 18 months for one to become available. Several candidates have entered clinical trials but previous efforts to make vaccines against coronaviruses have been unsuccessful.

ESMH Scientist Paul DigardProfessor Paul Digard at the Roslin Institute in Edinburgh points out: “Coronaviruses are not the easiest to make a vaccine against. (…) I don’t think it will be as difficult as for HIV. However, it may not be as simple as for something like flu, where we have decades old, tried and trusted technology.”

Both Rezza and Digard are of the opinion that research into antivirals is more promising in the short term. “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,” says Digard.

When it comes to antivirals, we are not starting from scratch. Some of the drugs that are being tested on Covid-19 patients attack processes that are common in different types of virus. An example of one of these ‘generic’ drugs is the synthetic nucleoside analogue ribavirin, which interferes with viral replication. Other drugs, such as protease inhibitors, previously used against viruses like-SARS, HIV and Hepatitis C , are also being trialled against SARS-Cov-2.

Another promising approach involves using immuno-modulators, compounds that affect the patients’ response rather than the virus directly.

Professor Giovanni Rezza: “At the hospital Lazzaro Spallanzani in Rome we are testing (…) anti-inflammatory monoclonal antibodies against interleukin 6, that have been used successfully in the treatment of rheumatoid arthritis, and we have seen some encouraging results in patients that are in sub-intensive treatment.”

Similarly, as in the case of influenza, antivirals against SARS-CoV-2 are likely to be most effective when treatment is initiated early in the course of infection.

Professor Paul Digard warns: “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.”

Several groups in Europe are focussing their efforts on producing genetically engineered monoclonal antibodies that bind to specific regions of SARS-CoV-2 and stimulate the patient’s immune system to attack virus-infected cells. “This is a worthwhile strategy as they are fast to produce if they prove to be effective,” explains Rezza.“ The EU should not just be funding efforts to test these new products as soon as possible, but also, looking at ways to accelerate approval”.

At present there is no evidence to suggest that the virus will disappear as the weather gets warmer in the Northern hemisphere. It is also unclear whether it could adopt a cyclical pattern. “It is important to realize that we are unlikely to get rid of it quickly (….). We need both short- and long-term fixes for this,” says Digard.

Because the clinical spectrum of Covid-19 varies from asymptomatic to requiring support in an intensive care unit, it will be extremely useful to understand what factors determine whether a patient experiences mild symptoms or likely to become severely ill. Understanding the immune response of patients that experience a mild form of the disease could guide the development of new therapies that target the host’s immune response rather than the virus directly (immuno-modulators).

Further research into the origin of SARS-CoV-2 will help determine the risk of future re-emergence events. Evidence to date indicates that SARS-CoV-2 is most similar to other coronaviruses found in bats, but there are sufficient differences between the genetic sequences to suggest that the virus went through an intermediate host before infecting humans. Ultimately, “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,” concludes Digard.

Useful links
As the world struggles to contain the coronavirus pandemic, the EU is supporting efforts to develop vaccines and effective treatments as soon as possible.

Related Content:
A scientist’s opinion : Interview with Professor Giovanni Rezza on tackling the Covid-19 pandemic
A scientist’s opinion : Interview with Professor Paul Digard on research efforts to develop treatments against Covid-19