In the quest to help end the current pandemic, a treatment for Covid-19 could be considered one of the holy grails.
But developing new treatments is typically a lengthy process. It can take more than a decade to go from a scientist’s eureka! moment in the lab to an approved drug that's available on the market, particularly if extremely large quantities are needed, like in the case of Covid-19.
But there is a potential accelerated way to find an urgently needed treatment: If scientists can repurpose an existing, approved treatment for another disease, or one that has already been through rigorous clinical testing, they can potentially bypass some of the early, preclinical testing phases.
The novel coronavirus pandemic has set scientists all over the world down this drug development track, including those at the Janssen Pharmaceutical Companies of Johnson & Johnson. In fact, Marnix Van Loock, Scientific Director and R&D Lead of Emerging Pathogens, Global Public Health, and Sandra De Meyer, Senior Director and Head of Clinical Microbiology and Immunology, are working together with the Rega Institute for Medical Research, part of the Catholic University of Leuven in Belgium, to screen a drug repurposing library of thousands of existing drug compounds.
To expedite the search for potential Covid-19 treatments, Johnson & Johnson and the Biomedical Advanced Research and Development Authority have expanded their partnership to accelerate Janssen’s ongoing work in screening compound libraries, including compounds from other pharmaceutical companies. By testing the antiviral activity of these compounds against SARS-CoV-2, the virus that causes Covid-19, they hope to identify an existing, proven-safe drug that could have the potential to be turned into a new treatment for the virus.
We sat down with Van Loock and De Meyer to learn more about their unique jobs as molecular investigators—and the potential impact their work could have on the trajectory of the current pandemic.
Can you tell us more about what exactly is included in this Janssen “molecule library”?
Van Loock: It contains chemical molecules of approximately 5,000 approved drugs with sufficient clinical safety data that can be used immediately in Covid-19 patients.
It also contains compounds that are currently in clinical development, but for which we’ve already generated safety data.
What’s the screening process like?
Van Loock: Each of these compounds will be evaluated for antiviral activity against the novel coronavirus (also known as SARS-CoV-2), which we’re doing in close collaboration with Professor Johan Neyts and his team at the Rega Institute.
We have access to a virus strain that has been isolated from an infected patient in the current coronavirus outbreak, so we can assess the potential antiviral activity of the compounds in the library against this novel coronavirus.ShareDid you like reading this story? Click the heart to show your love.
We have access to a virus strain that has been isolated from an infected patient in the current coronavirus outbreak, so we can assess the potential antiviral activity of the compounds in the library against this novel coronavirus.
Can you explain how an effective drug might work?
De Meyer: Viruses enter the cells of an infected patient and produce copies of themselves within these cells. An effective antiviral drug can inhibit that replication process. By inhibiting the replication, a drug can buy the body time to generate an immune response and clear the virus.
In our lab, cells are infected with the virus in the presence or absence of different compounds from our library. This helps to determine whether any of these compounds can directly prevent replication of the virus.
How do you determine which compounds to screen first?
Van Loock: The first stage is screening existing drugs that are used in patients now. And we aren’t limiting ourselves to just compounds that have been shown to be effective against other infectious diseases. We’re also testing compounds that were developed in fields like oncology, neuroscience or immunology to see if they could be effective against the virus.
It’s not just about getting information on compounds that are active against the virus, but also finding out which ones aren’t active.ShareDid you like reading this story? Click the heart to show your love.
In a second wave of screening, we will include compounds that aren’t on the market, but have been shown in the scientific literature to have activity against other coronaviruses. These compounds are still in a very early stage of drug discovery.
De Meyer: In addition, whenever there is information circulating about a potential coronavirus treatment—whether it’s a rumor that a compound is effective against the virus or a scientific publication hinting at antiviral activity—we try to confirm whether the information is true.
It’s not just about getting information on compounds that are active against the virus, but also finding out which ones aren’t active.
If you find a promising compound during the screening, what’s the next step?
De Meyer: We will first gather all existing information on the compound to evaluate whether it would be suitable to further explore in a clinical study.
Since there is already a framework in place for clinical development, if promising antiviral compounds are identified, then the clinical development team could immediately start designing and executing a clinical study.
Van Loock: For each compound in the library, there is already a safety data package, which describes the use of that molecule in humans. If we find something interesting that shows activity against SARS-CoV-2, that safety data immediately shows us whether or not it could be tested in a clinical study for Covid-19.
It sounds like cutting down on the time it takes to get a drug into the pharmacy is one advantage of this library, correct?
De Meyer: Yes. The thing that makes drug development a years-long process is that you have to demonstrate that the drug is safe to be used in patients. With these compounds, we already know they're safe.
The thing that makes drug development a years-long process is that you have to demonstrate it’s safe to be used in patients. With these compounds, we already know they're safe.ShareDid you like reading this story? Click the heart to show your love.
Van Loock: Depending on the type of drug you find, it may require reformulation. If you find one that mainly targets the liver, for example, that would be less ideal because Covid-19 is a respiratory disease. So a reformulation may be required, but that’s still less time than it would take if we were starting from scratch.
So you could theoretically compress the timeline from years to ... what?
Van Loock: With the screening effort up and running, and because of the unique partnership we have with the team at the Rega Institute, then it could be potentially months rather than the typical years.
De Meyer: This is also where we can tap into the strengths of Johnson & Johnson. There’s a clinical development team already ready to go, and we’re part of that team, so the transition can go very smoothly.
How optimistic are you that you can pinpoint an effective treatment?
Van Loock: We are cautiously optimistic.
We’re faced with several challenges, the biggest one being that this is a new disease, so there is a lot to learn in a very short time frame.
De Meyer: The degree of collaboration that we see—people making themselves available on weekends and evenings—it’s incredible. We’re asking a lot from people at the moment, and everyone’s so eager to help find a treatment for Covid-19 patients.