Researchers at the Perelman School of Medicine at the University of Pennsylvania and the University of Maryland School of Medicine have identified a powerful combination of antiviral drugs to treat COVID-19.
They found that combining the drug brequniar with remdesivir or molnupiravir inhibited the virus in human respiratory cells and in mice, according to Medical Xpress.
The findings, published in the journal Nature, suggest that these antiviral drugs are more powerful when used in combination than individually.
The study’s principal investigator and lead author Dr. Sara Cherry said they have not yet been tested in human trials, but the combinations of these drugs have the potential to become very promising COVID-19 treatments.
“Identifying combinations of antivirals is really important, not only because doing so may increase the drugs’ potency against the coronavirus, but combining drugs also reduces the risk of resistance,” she said.
COVID-19 continues to infect millions of people so there is an urgent need for therapeutics to treat the disease. Moreover, the pandemic has been amplified by the emerging variants that may evade protection induced by vaccines.
Dr. Cherry and her team screened 18,000 drugs in search of antiviral activity, using live coronavirus infection in human respiratory epithelial cells, as the virus mainly targets the lung cells.
The authors identified 122 drugs that showed antiviral activity and selectivity against the coronavirus, including 16 antivirals that are in clinical use. Among those 16 antivirals were remdesivir and molnupiravir – both of which have been approved by the Food and Drug Administration (FDA). They also identified a nucleoside biosynthesis inhibitor, called brequinar, which is an experimental antiviral drug.
A nucleoside biosynthesis inhibitor works by blocking some enzymes from making nucleosides, preventing the virus from being able to “steal” RNA building blocks and replicate.
Currently, brequinar is being tested in humans as a COVID-19 treatment. It is also being tested as a potential combination therapy for some cancers.
Dr. Cherry explained, “We thought that using these nucleoside analogs while also reducing the levels of the host’s nucleoside building blocks might work together to super destroy the virus. It is really amazing that when you combine them, the virus is completely dead.”
The researchers tested the combination of these drugs in lung cells in mice and found that it was highly effective against multiple variants of the coronavirus, including the highly contagious Delta strain.
The investigators, who are now in the process of testing the drugs against the Omicron variant, also found that Paxlovid (nirmatrelvir and ritonavir) could be combined with remdesivir or molnupiravir for an “additive” effect against the deadly virus.
These drug combinations will now be tested in humans.
The study’s co-principal investigator Dr. Matthew Frieman said, “As new strains of the virus emerge, the need for new treatments will remain critical. We now know that there are a number of powerful drug combinations that have the potential to alter the trajectory of the virus.”
