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Washington : According to a study, combining the antivirals remdesivir and molnupiravir with the investigational medication brequinar prevents the SARS-CoV-2 virus, which causes COVID-19, from reproducing in lung cells and animals.
According to the study, which was just published in the journal Nature, these medications are more potent when taken together than when taken separately. The combinations of medications revealed in the study have the potential to become very promising COVID-19 therapies, according to the researchers, even if they have not yet been tested in clinical trials. “Identifying combinations of antivirals is incredibly essential, not only because it may boost the medications’ potency against the coronavirus, but it also minimises the possibility of resistance,” said Sara Cherry, a professor at the University of Pennsylvania in the United States, who led the study.
The need for therapies to treat COVID-19 is still urgent, according to the researchers, which has been exacerbated by the threat of additional variations that may avoid immunizations. They used live SARS-CoV-2 infection in human respiratory cells to screen 18,000 medicines for antiviral efficacy, because the virus’s main target is the lungs. The researchers discovered 122 medicines with antiviral activity and selectivity against the coronavirus, including 16 nucleoside analogues, the most commonly used class of antivirals in clinical practise.
Remdesivir, an intravenous injectable approved by the US Food and Drug Administration (FDA) to treat COVID-19, and molnupiravir, an oral pill approved in December last year, were among the 16 drugs. A panel of host nucleoside biosynthesis inhibitors, including the investigational medicine brequinar, was discovered among the 122 therapeutic candidates.
Nucleoside biosynthesis inhibitors hinder the virus from multiplying by preventing the body’s own enzymes from generating nucleosides. Brequinar is currently undergoing clinical trials as a COVID-19 medication and as part of a potential cancer combo therapy. Cherry and colleagues hypothesised that combining brequinar with a nucleoside analogue like remdesivir or molnupiravir would provide a “synergistic” impact against the virus.
When the combined effect of two or more medications is higher than the sum of their individual effects, synergistic interactions occur. “We assumed that employing these nucleoside analogues in conjunction with lowering the levels of the host’s nucleoside building blocks would act together to super kill the virus,” Cherry explained. “It’s wonderful because the virus kills completely when you combine them,” she concluded. The drugs were tested in lung cells and animals, and were found to be highly efficient against a range of coronavirus strains, including the Delta strain.
The medications are currently being tested against Omicron by the team. Paxlovid, an oral antiviral that was recently approved by the FDA, could be used with remdesivir or molnupiravir for a “additive” impact against SARS-CoV-2, according to the researchers. These drug combinations would then be tested in clinical trials as the following stage. “As new strains of the virus arise, the need for novel treatments will remain critical,” said Mathew Frieman, a co-principal investigator of the study from the University of Maryland School of Medicine. Frieman continued, “We now know that there are a variety of powerful treatment combinations that have the ability to alter the virus’s trajectory.”
