Scientists from the University of Pennsylvania found a powerful combination of antivirals to treat COVID-19.
They found combining the drug brequniar with remdesivir or molnupiravir—both approved by the U.S. Food and Drug Administration for emergency use—inhibited the SARS-CoV-2 virus in human respiratory cells and in mice.
Though they have not yet been tested in clinical trials, the combinations of drugs identified in their study have the potential to become very promising COVID-19 treatments.
The study is published in Nature and was conducted by Sara Cherry et al.
In the study, the team screened 18,000 drugs in search of antiviral activity, using live SARS-CoV-2 infection in human respiratory epithelial cells, because lung cells are the major target for the virus.
The researchers identified 122 drugs that showed antiviral activity and selectivity against the coronavirus, including 16 nucleoside analogs—the largest category of antivirals that are used clinically.
Among the 16 were remdesivir, which is given by injection into a vein and has been approved by the FDA to treat COVID-19, and molnupiravir, an oral pill that was authorized for use in December.
Also among the 122 drug candidates, the researchers identified a panel of host nucleoside biosynthesis inhibitors, including the experimental drug brequinar.
Nucleoside biosynthesis inhibitors work by blocking the body’s own enzymes from making nucleosides, which prevents the virus from being able to “steal” RNA building blocks and replicate.
Brequinar is currently being tested in clinical trials as a COVID-19 treatment and as part of potential combination therapy for some cancers.
The team says that combining brequinar with a nucleoside analog, such as remdesivir or molnupiravir, could work “synergistically” to create a more potent effect against the virus.
The researchers tested the drugs in lung cells as well as in mice, and found that these combinations were highly effective against multiple strains of the coronavirus, including the Delta variant.
The team is now in the process of testing the drugs against Omicron.
Additionally, the researchers found that Paxlovid—an oral antiviral that was also recently authorized by the FDA—could be combined with remdesivir or molnupiravir for an “additive” effect against SARS-CoV-2.
The next step would be for these drug combinations to be tested in clinical trials.
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