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Researching the novel coronavirus in the urgent search for solutions
Published 02 April 2020
“Pandemics have occurred throughout human history and they are inevitable,” explains John Young. As the Global Head of Infectious Diseases, Roche Pharma Research & Early Development, he knows quite a bit about pandemics and viruses. However, a global challenge like COVID-19 has not been seen in recent history and therefore requires a modern approach to combat it.
He cannot stress enough the immense value of partnership in a time when precious resources cannot be spared and the race is on to avert further disruptions to communities across the globe. Now is not the time to turn inward. With so many brilliant scientists racing to find a solution to the novel coronavirus, it is now more important than ever to team up against the common enemy for the benefit of the world.
In an interview, he shares his insights on the biology of the virus and whether a cure may be possible.
It is still early in terms of the COVID-19 outbreak with many countries still to hit the peak number of cases. Have scientists been able to find out more about the genetic make-up of the coronavirus and how it works?
The complete genome sequence of the SARS-CoV-2 virus (from a Wuhan patient isolate) was determined and made public almost immediately after the initial outbreak. Virus genome sequences have subsequently been characterised from different parts of the world. The virus genome is very similar and almost 79% identical to that of the original SARS virus.
Does that potentially tell us how it can be tackled or treated?
The sequence provides a blueprint for discovering and developing new drugs against the virus. The virus does not appear to be changing rapidly and this is encouraging news for vaccine development since it suggests the possibility of developing a single vaccine that can protect against all versions of the virus.
How are you working with external partners on programmes focused on COVID-19?
We initiated an internal research programme to develop drugs against SARS-CoV-2. We also initiated an external collaboration with Nevan Krogan and his team at the University of California San Francisco (UCSF) and are exploring other collaboration and partnership opportunities. We established an internal review team to rapidly evaluate the large number of potential collaboration and partnering opportunities that we have received.
Two specific examples would be in our support for the efforts being done by Nevan Krogan and UCSF's Quantitative Biosciences Institute (QBI) Coronavirus Research Group. The goal of the programme is to characterise the interactions between the virus and cellular proteins with the goal of identifying new therapeutic approaches.
In the short-term, this approach has identified targets of FDA-approved and clinical stage drugs that could be effective against this disease. In the longer term, these studies are expected to uncover novel drug targets that could then become the focus of new drug discovery and development campaigns. This collaboration builds on a long-standing relationship that we have with the Krogan laboratory to use this technology to discover new drug targets.
What could these efforts mean for healthcare workers and clinicians in the frontline?
If FDA-approved drugs are found to be effective against the virus this could have immediate utility for protecting/treating healthcare workers against COVID-19. We are currently evaluating which drugs we will investigate, and it is too early to speculate on which FDA approved medicines will be effective against this disease.
What about the basic biology of the virus? Are the types of approaches drug developers are pursuing to combat it? Do you see effective treatments coming through quickly with these approaches?
Several existing clinical stage drugs are being tested in clinical trials for their efficacy in treating SARS-CoV-2/COVID-19. If one or more of these drugs proves to be effective, this could lead to a rapidly available treatment for this disease. If not, new drugs will need to be developed, a process that takes many years.
Coronaviruses have an RNA genome, encoding nearly 30 viral proteins, some of which are produced initially as one long protein chain, like a "ribbon". One virus protein, a so-called protease, acts as a pair of molecular scissors to cut this ribbon into separate pieces. This results in the separate virus proteins that are needed to support virus replication. Another virus protein, a so-called polymerase, is responsible for making copies of the virus genome. The viral polymerase and protease proteins are the two most attractive drug targets that we know about so far.
Right now, there is a scramble for a vaccine against COVID-19. Many would question why big pharmaceutical companies don’t invest enough in developing vaccines until it is too late.
A vaccine could be a very promising approach to tackle COVID-19. Indeed several experimental vaccines have been developed at breakneck speed and have rapidly entered clinical trials. The challenge for a vaccine approach is that we still do not know which parts of the host immune response are the most important for vaccine efficacy. Because this is a newly emerging virus, it would not have been possible to generate an effective vaccine prior to the pandemic.
As a virologist by training, what does this pandemic tell you?
Pandemics have occurred throughout human history and they are inevitable. In this case, it appears that a virus, which normally resides in bats, was transmitted either directly or indirectly to humans and has spread quickly across the globe. Densely packed human populations and extensive global travel networks have certainly contributed to the pace at which this pandemic has progressed.
Disclaimer: Roche is not actively engaged in vaccine research and development activities for SARS-CoV-2.
Learn more about John Young and Infectious Diseases at Roche Pharma Research & Early Development
In conversation with John, we explore a range of topics including his professional journey, why Roche is in an excellent position to tackle infectious disease solutions, and how his group is aiming to develop novel antibiotics to combat drug-resistant bacterial infections including a cure for chronic hepatitis B virus infection.