Creating a Menu of Assays against COVID-19
Regina Kelder

Creating a Menu of Assays against COVID-19

How an immunologist is working to find viable drugs against COVID-19   

There are a lot of analogies one could use to describe the COVID-19 research that Claire Richards performs at her Portishead, UK lab. The one she settles on is puzzle solving.

Claire, a trained virologist and immunologist based at Charles River Laboratories creates assays, i.e. the solution to the puzzle that detects the presence of virus when added to lung epithelial cells which contain a matching piece of the puzzle, a target for SARS-CoV-2. Extra pieces can be added which help to build the picture—and identify viral genetic material and then amplify it. If the virus is in cells, the reagents should detect it and vice versa.

Claire’s team is developing a number of cell-based assays as screening tools for COVID-19 drugs that patients desperately need. Because their laboratory is only a Biosafety Level 2 lab—the highest being 4—they are limited in what kinds of viruses they can use to set up their assay. The SARS-CoV-2 virus—a Category 3 virus—is out, but the team can use influenza virus or respiratory syncytial virus (RSV) as well as other laboratory strains of coronaviruses that attack the cells lining the lung in much the same the way SARS-CoV-2 does. The assays take about 3-5 days to develop and determine whether the test compound is active against the virus. Those compounds showing positive effects can then be passed on to our partners with a BSL-3 lab, to set up COVID-19 assays saving time and money for the more expensive Level 3 labs.

Ever since the pandemic hit Europe and forced most countries there into lockdown, Claire and her six colleagues working in the seaside community of Portishead, UK, have been doing the opposite, laboring under conditions that now require them to work at least six feet apart. With more than 160 treatments and vaccines in R&D—and no approved treatments or vaccines available at this time—the work being carried out by researchers is not just essential but a race against time. Against the 5.6 million cases worldwide, and 350,000 dead—frightening numbers that rise daily—it certainly feels like the virus is winning.

But Richards is a scientist and scientists are all about problem solving. She is happy to be able to do her part because with vulnerable people surrounding her she feels the need to do something.

“I have a 25-year-old niece who has cystic fibrosis,” says Richards. “If she were to get [COVID-19] I would be pretty damn certain she wouldn’t survive.”

A viral career

Richards has been surrounded by viruses her entire career. She did her PhD on influenza viruses and then crossed over to herpes, particularly Herpes Simplex serotype 1 (HSV-1). Because HSV 1 is virus that invades our mucosal sites, Richards began looking at mucosal vaccines that modulate the immune system. As it turns out, immune modulation is also a key factor in people with COVID-19, who can find themselves at war not only with the virus but with a deluge of out-of-control immune cells. How to alleviate this cytokine storm has lately become a focus of not just the Portishead site but other laboratories as well.

The in vitro viral assays that Richards’ team works on have become a critical piece in determining how to treat COVID-19 effectively. They take epithelial cells found in lung tissue, expose it to virus and if the virus infects the cell and causes it to die they have a measure of how the cells react. When they take those same virus-exposed cells and treat it with a drug compound, if the virus is killed they know the drug could be a good candidate for preventing infection of the cells or replication of the virus within the cells in a real-world setting.

The work Claire’s team is doing is at the very early stages—the “test tube” stage—long before a person is dosed in a clinical trial. But it is a vital step in identifying the first flickers of a game-changing drug.

“This pandemic is affecting everyone’s lives. There is so much uncertainty,” says Claire. “We have to find some sort of solution as quickly as possible. For me, to try and answer these questions is what drives me and my team.”