COVID Stories: Drug Discovery Unit led contributions to worldwide effort to tackle coronaviruses (Part 3)

Alongside this, scientists are continuing to contribute to the worldwide efforts to tackle COVID-19. Some projects are progressing while others are just starting up following recent funding awards. What is it like as a scientist working with social distancing and additional measures in place in the research laboratories? How has the working day changed?

Part 3: Drug Discovery Unit

Internationally renowned scientists bring their unique position of bridging the gap between academic scientific research and commercial drug discovery and development to tackle SARS-CoV-2 and future coronaviruses.

In the 14 years since it was established the Drug Discovery Unit (DDU) has developed two areas of activity, infectious diseases of low and middle income countries and the Innovative Targets Portfolio (ITP) covering diseases such as Alzheimer’s disease, cancer and psoriasis. As the coronavirus pandemic developed, the management team within the DDU knew they had the skills and expertise to assist.

At the same time, many organisations were redirecting their focus to provide financial support to develop understanding of SARS-CoV-2 and how to treat it. The Bill and Melinda Gates Foundation was one of those organisations. They have supported a number of research projects in the DDU. In recent years this includes funding to tackle tuberculosis and to develop a male contraceptive. The Foundation approached the DDU to ask if they would be interested in working on coronaviruses.

Professor Paul Wyatt, Head of the DDU, explained, “We had that discussion and felt that this is such an important activity that we really have to be part of. The DDU is about tackling unmet medical need for important diseases.”

Tackling the COVID problem from a drug discovery perspective

Currently, the two main drugs used to treat SARS-CoV-2 were not made to treat SARS-CoV-2. “We're dependent on something that was developed for Ebola that just happens to have some effect but it has side-effects, and dexamethasone which is a broad-spectrum drug that knocks down the inflammation. It works, but it's not a particularly good answer. It’s not very specific” commented Professor David Gray, Head of Biology in the DDU. “That's the point where we became interested in doing something and that's the point where people at the COVID-19 Therapeutics Accelerator, initiated by the Bill & Melinda Gates Foundation, Wellcome and Mastercard, were starting to think the same way and putting money in place that allows us to actively try and do something.”

There are two key approaches to develop new treatments, firstly repositioning existing drugs which covers antivirals to combat the virus and drugs that will alleviate the symptoms. The other is to develop brand new medicines. The DDU is working in both these areas with several collaborative projects underway. This research not only covers the current coronavirus (SARS-CoV-2) but future coronavirus strain that may appear.

“This coronavirus may go. We may find a vaccine for it, but it looks like coronaviruses are going to be an ongoing problem. These are a family of viruses that we are going to have to be involved with in the long term,” explained David.

The journey of a drug from bench to bedside is long and perilous. It can take years and many fail along the way. However, there is a need to be prepared and have a drug on the shelf ready to go as Paul explains, “By the time we get a drug to be ready for clinical use from a very early programme, hopefully COVID-19 is going be solved. However, it is essential to have drugs on the shelf that can be used for future strains of coronaviruses. Having drugs that can be used at the beginning of an outbreak to suppress it quickly in a local environment, gives the tools to help stop future pandemics.”

Building on existing relationships and creating new collaborations

The DDU coronavirus projects have involved existing and new collaborations. They include local ones involving other research groups within the School of Life Sciences including with Dr Yogesh Kulathu in the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit (MRC-PPU) and Professor Vicky Cowling from Gene Regulation and Expression. Further afield, there are programmes with the Scripps Institutes ReFRAME collaboration, the Centre for Virus Research in Glasgow, and a Europe wide consortium that involves Dundee spin-out ExScientia and the University of Leuven who are both new to working with the DDU.

“A lot of the interactions we're building from scratch,” states Paul but in doing so, it has brought new ways of working from the traditional way that often involved international travel. “In some ways it is more effective to have meetings with multiple partners in multiple places over the Internet. We've become completely dependent on that. It's a lifeline. It's a very different way of working.”

“Establishing these new partnerships and projects within such a short time frame is no mean feat. Having partners in different time zones means video -meetings at all hours. It takes commitment and energy but is certainly easier that getting on an airplane.  I think business development will change for the longer term,” added Dr Julie Brady, Business Development Manager for the DDU.

In addition, the expertise of members of the DDU have been called upon at a national level including David Gray who is involved in the establishment and running of the Glasgow Lighthouse Lab. This role was undertaken on top of the ‘day job’.

Recommencing existing drug discovery projects

In the past two months, the DDU laboratories have fully reopened allowing scientists to return and recommence the work they were undertaking before lockdown. Capacity has been built back up and staff have had time to adapt to the new safety measures now in place. However, not everyone is back which adds new challenges as David explains, “The biggest challenge is probably the fact that we will not be coming back with them because there is actually little justification for the management team actually being on site.”

David continues, “The people management is going to be more difficult and certainly working remotely is not something that I would want to do in the long term. I just don't like it. I need to be close to where the data is being generated and all the stuff that’s going on. I need to be able to walk up a corridor and spot people chatting and be able to gauge how they're feeling and all that stuff. I can't do that remotely. It doesn't feel good.”

“I think it's harder to run our projects, especially if you've got multiple people in meetings, because I think the interactions are less natural. However, we are getting better at running online meetings and the technology is getting better. I miss going into work and talking to people about our work and how they are getting on. However, these issues are minor compared to the terrible toll this disease is causing in the world, so we just have to get on with it. It’s great the team are back in the lab and we are beginning to make progress on multiple fronts. The team has been excellent in its planning and eagerness to get back in the lab to work a safe and productive way.” concludes Paul.