Combining the experimental drug brequinar with the antiviral drugs remdesivir or molnupiravir, whose use has already been approved by the FDA (United States Food and Drug Administration) and the EMA (European Medicines Agency) for the treatment of COVID-19, has demonstrated its efficacy in inhibiting the SARS-CoV-2 coronavirus in a study that has been carried out in human respiratory cells and in mice, which has been led by scientists from the Perelman School of Medicine of the University of Pennsylvania and the University of Pennsylvania School of Medicine. the University of Maryland (USA).
The researchers have verified that the combination of these antivirals is capable of blocking the replication of SARS-CoV-2 in lung cells and in mice. The results of their study, which have been published in Nature, suggest that these drugs act more potently when used in combination than when they are administered separately, and if their efficacy is confirmed in clinical trials, they could become a promising treatment against COVID-19.
“Identifying combinations of antivirals is really important, not only because doing so can increase the potency of anti-coronavirus drugs, but because the combination of drugs also reduces the risk of resistance,” said Dr. Sara Cherry, professor of pathology and Laboratory Medicine at Penn, who led the research with David Schultz, MD, technical director of the Penn High-Throughput Screening Core, and Matthew Frieman, MD, of the Center for Pathogen Research at the University of California School of Medicine. Maryland, and collaborators at the National Institutes of Health.
New treatment options against COVID-19
To respond to the threats posed by the new variants of the coronavirus that, as occurs with delta or omicron, can evade the protection of vaccines, it is necessary to find drugs that are effective against this pathogen. To do this, these scientists evaluated 18,000 drugs to find out their antiviral activity in live SARS-CoV-2 infection in human respiratory epithelial cells, since lung cells are the main target of the virus.
By testing the drugs on lung cells and mice, they found that these drug combinations were highly effective against multiple strains of the coronavirus, including the delta variant.
They found 122 drugs that showed antiviral activity against SARS-CoV-2, including 16 nucleoside analogs, the largest category of antivirals used in clinical practice. Among these 16 was remdesivir, which is administered intravenously to treat COVID-19, and molnupiravir, an oral pill authorized a few months ago by health authorities.
The researchers also identified a panel of inhibitors of host nucleoside biosynthesis, including the experimental drug brequinar. These types of drugs act by blocking the body’s own enzymes so that they do not produce nucleosides, which prevents the virus from stealing the basic components of RNA and replicating. Brequinar is currently being tested in clinical trials as a treatment for COVID-19 and as part of a possible combination therapy for some types of cancer.
Cherry explained: “We think that using these nucleoside analogs and reducing the levels of the host’s nucleoside building blocks could work together to destroy the virus.” And she adds: “It’s really amazing that when you combine them, the virus is completely dead.”
The study authors decided to test the drugs in lung cells and mice and found that these combinations were highly effective against multiple strains of the coronavirus, including the delta variant, and are now working to test the drug cocktail against omicron. They also discovered that the oral antiviral Paxlovid could also be combined with remdesivir or molnupiravir to achieve an “additive” effect against the coronavirus.
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