Researching treatments for Covid-19

Last March, myself and several colleagues from The Liverpool School of Tropical Medicine(LSTM) were made ‘key workers’ in the fight against Covid-19 through scientific research. Our role, working with key collaborators, was to screen compounds against SARS-CoV-2, as there is a clear need for treatments and prophylactics with efficacy against the virus. Also, it is important to note that when this work began, there were no vaccines available and no vaccines in the pipeline.

Currently there remain millions of people who have severe symptoms from a Covid-19 infection and we need to know how best to treat those people who do become ill. Although the vaccination programme is well underway and proving to be highly successful at lowering death rates and the requirement for hospitalisation within the UK, effective treatments against Covid-19 have to be part of the strategy.

Whilst the country went into its first lockdown, we at LSTM became busier than ever. We had to prepare our laboratories for the new drug-screening work, as well as learn the different techniques and protocols we would be employing to work with this novel containment level (CL) 3 laboratory virus. CL3 laboratories are strictly controlled, government-registered labs with very specialist set-ups and highly trained staff. The main purpose of CL3 laboratories is to protect staff when handling dangerous pathogens (such as Covid-19) for the purposes of research. I had predominantly worked with bacterial pathogens prior to this work, others worked in a chemistry setting, therefore new training, risk assessments and vital preparation were required prior to beginning any drug-screening assays with Covid-19.

Why is Covid-19 difficult to work with? Covid-19 has been classed as a hazard group 3 (HG3) pathogen by the UK Advisory Committee on Dangerous Pathogens. There are 4 classifications of hazard groups, HG1, HG2, HG3 and HG4. HG3 pathogens are defined as biological agents that can cause severe human disease, may be a serious hazard to employees and may spread to the community. Examples of other HG3 pathogens include HIV, Dengue, Tuberculosis (TB) and Yellow Fever. HG3 pathogens must be worked with and handled within a CL3 laboratory.

With my background in TB, I have worked in CL3 laboratories for nearly a decade. As such, my initial role was to train colleagues who work in different laboratory environments to work safely with Covid-19, within this high containment setting. Like Covid-19, TB is predominantly a respiratory disease, which remains a leading cause of global death from a single infectious agent. My background in drug discovery for TB armed me with many of the skills required for this work. Having worked in CL3 labs in South Africa with drug resistant strains of TB, as part of my Churchill Fellowship, I was well adapted to wearing masks, specialist PPE and handling pathogens of unknown virulence.

Within our study, we focused on some newly developed compounds, as well as screening drugs that have already been granted license for use in humans. This would represent the quickest route to the clinic if ‘hits’ were identified. An example of this is Remdesivir. Remdesivir is an anti-viral drug used to treat hepatitis C and, in early studies against Covid-19, it was reported that it ‘was superior to placebo in shortening the time to recovery in adults who were hospitalised with Covid-19’: as such it became the first repurposed drug to be licenced for treating Covid-19.

Our drug screening assay was entirely cell-based, developed to be as rapid and low cost as feasible. As well as the data produced, it is hoped the methodology we developed to carry out the screening will support larger-scale drug discovery in the coming months, as researchers strive to find compounds to treat those who are unwell from Covid-19. Our data has been submitted as part of peer-reviewed publications and will soon be freely available.

Read the research paper co-authored by Samantha