As San Diego County’s COVID-19 cases decline and vaccination numbers increase, local researchers are still engaged in the search for treatments for the disease and have found several potential treatments in existing medications, with long-range implications for treating not only the current pandemic but also any in the future.
The results of a Scripps Research study published June 3 in Nature Communications identify 90 known drugs that demonstrate antiviral activity against COVID-19.
Of those, four drugs approved by the U.S. Food and Drug Administration and nine others in various stages of development for use on other diseases were found to have potential to be repurposed as COVID-19 therapies.
Arnab Chatterjee, one of the study’s authors and vice president of medicinal chemistry at Calibr, the drug discovery division of Scripps Research in La Jolla, said the existing drugs were found to “slow down the replication” of SARS-CoV-2, the virus that causes COVID-19.
“The really interesting part,” he said, “is that those molecules … work in one or multiple different cellular systems, acting directly with the protein that’s encoded by the virus” and inhibiting the virus’s replication “through affecting the host cells, the cells that are actually being taken over by the virus to propagate its growth.”
The drugs screened in the study came from Calibr’s ReFRAME drug repurposing library, Chatterjee said. Those involved in the study tested more than 12,000 known drugs against SARS-CoV-2.
Chatterjee said the “value of drug repurposing is that one could imagine, at the onset of a pandemic or new disease, that one could take existing drugs already approved” for use in humans for testing on the new disease in clinical trials, as the drugs’ safety has already been established.
“First and foremost, I think safety is important,” he said.
“The second part that’s also important is understanding how the drug currently works, the way that it’s used or has been developed for, and whether or not that mechanism … [overlaps] with what we think would be involved in replication of the virus.”
Chatterjee said a set of 19 compounds, while not found to entirely inhibit replication of the virus, were found “to work to some extent,” especially when used with remdesivir, the only FDA-approved therapy for COVID-19.
“We do believe that in a world where you’re using drug combinations, an individual drug itself may not be very effective but it could be potentially combined,” he said.
The study shows “there are clearly some compounds that don’t work well on their own, but they do work well combined with something else,” he added.
Using a combination of drugs, he said, increases the effectiveness of the treatment and broadens options to fight variants of a virus, which develop over time as a virus “either changes the way that it enters cells” or becomes resistant to drug therapies.
Chatterjee said “we really need drugs to be able to not only be more effective treatments when combined but trick the virus into being unable to develop drug resistance, which obviously you can only do once you add more than one drug into a cocktail.”
“These drugs could potentially be used in the context of future coronavirus infections,” he said. “The fact that the drugs work in inhibiting replication of the virus in and of itself could be useful for future pandemics.”
A more important implication, however, is that the study “allows us to be able to understand the drugs,” Chatterjee said. “We need to have those systems to be able to then optimize and make new drugs … that could be much more effective treatments.”
“It’s really about tailoring drugs, making them really fit for purpose,” he said. “You can’t do [that] unless you have all of the right systems in the lab to really understand [if we’re] actually making better compounds.”
To that end, Chatterjee and his colleagues are continuing to profile and test the drugs and compounds discovered. “We want to make sure for anything we put into clinical development that the compounds work well against multiple systems, so it adds to a level of confidence” for use in humans, he said.Original Source