The discovery of drugs that may be effective at inhibiting the spread of SARS-CoV-2 has spurred researchers at Yale University in New Haven, CT, to trial a new treatment for COVID-19, the disease caused by the new coronavirus.
The list of possibly effective drugs appears in the journal Nature and derives from an analysis of over 12,000 potential candidates.
The importance of repurposed drugs
The sudden emergence and rapid spread of SARS-CoV-2, coupled with its significant mortality rates, has forced governments worldwide to impose numerous emergency measures that have had a significant effect on social, economic, cultural, and political practices.
While these emergency measures have been effective at reducing the infection rate, in the absence of a vaccine or effective treatments, governments will likely continue to impose them as the virus begins to re-spread following the easing of the emergency measures.
Although researchers worldwide are making great efforts to develop an effective vaccine, they may not be able to attain one until next year.
Furthermore, the development of new antiviral treatments can, according to the authors of a 2020 article in Nature, take more than 10 years.
One way of responding to this extended time frame and the severe adverse effects on society of periodically imposing emergency measures is to look to drugs that have received approval to treat other diseases.
The current leading COVID-19 antiviral — remdesivir — is one such repurposed drug. However, given the novelty of SARS-CoV-2, research on effective antivirals is still ongoing.
Scientists might still identify more effective previously available antivirals, or other drugs that, when used in combination with other antivirals, increase overall efficacy.
Moreover, given the global nature of the pandemic, the availability of alternative antivirals may be valuable where demand stretches the supply of drugs, even if their effectiveness varies.
13 promising candidates
To further identify potentially effective antiviral drugs against SARS-CoV-2, the authors of the study in Nature analyzed a database of around 12,000 drugs that have already undergone different clinical trials and in vitro analysis.
Because the drugs in the database have already received screening and approval for effectiveness, safety, and availability, scientists can reduce the time it takes to develop potential COVID-19 treatments.
The researchers identified 100 drugs from this database that showed antiviral properties in response to SARS-CoV-2 in cells in the laboratory. Of those, they zeroed in on the 21 that seemed the most promising.
The researchers then tested those 21 drugs at various doses to assess which ones retained antiviral activity at concentrations that did cause too much damage to the cells.
Based on the results of these tests, they identified 13 drugs that showed clinically significant effects.
At the top of the list of potential candidates was LAM-002A 9 (apilimod), a drug used to treat follicular lymphoma and autoimmune diseases.
Now, a partnership between Yale University and the biopharmaceutical firm AI Therapeutics, who own the rights to LAM-002A, has proposed a phase II trial to assess its effectiveness at inhibiting SARS-CoV-2 in humans. The team expects the trial to involve 142 participants.
As well as being a potential treatment in its own right, AI Therapeutics believe that LAM-002A could improve the effectiveness of remdesivir. They have based this theory on their own unpublished data and recent data from the Scripps Research Institute.
According to Prof. Murat Gunel, who specializes in neurosurgery at Yale and is the chief scientific adviser to AI Therapeutics:
“LAM-002A holds promise to be a powerful new therapy for COVID-19 patients to prevent progression of the disease, hopefully avoiding the need for hospitalization.”
Until the publication of the trial results, scientists and other experts will not know how effective LAM-002A is likely to be. While it shows promise in a laboratory context, the critical factor is how it responds to the virus in humans.
However, if the drug does live up to its promise, the fact that scientists have already screened it for safety in other applications means that it should become available relatively quickly.