Combinations of antiviral drugs are highly effective in responding to COVID-19

Source: Science and Technology Daily

Science and Technology Daily Beijing, February 8 (Reporter Liu Xia) American scientists published a paper in the latest issue of the journal "Nature" that the nucleotide drug brequinar (brequinar), which is currently undergoing clinical trials against the new crown virus, is combined with remdesivir (remdesivir) or the new crown oral drug monapiravir (molnupiravir), which can inhibit the new crown virus in human respiratory cells and mice, and the combination of drugs is more effective than the use alone.

Sarah Cherry, one of the study leaders and professor of pathology and laboratory medicine at the University of Pennsylvania School of Medicine, said: "It is important to identify combinations of antiviral drugs that not only improve the effectiveness of the drug against COVID-19, but also reduce the risk of drug resistance. ”

Because lung cells are the main targets of the new crown virus, Cherry's team infected human respiratory epithelial cells with the new crown virus and examined the antiviral activity of 18,000 drugs. The researchers finalized 122 drugs that have antiviral activity against the new coronavirus, including 16 nucleoside analogues. These are the most clinically used classes of antiviral drugs, including remdesivir and monapiravir, both of which are approved by the U.S. Food and Drug Administration (FDA) for emergency use. The researchers also found a group of host nucleoside biosynthetic inhibitors, including brequinar. Nucleoside biosynthesis inhibitors prevent the body's own enzymes from producing nucleosides, thus preventing viruses from "stealing" RNA fragments and replicating them.

Cherey et al. hypothesized that combining buquina with nucleoside analogues would "synergistically" produce a more effective antiviral effect. The researchers tested the drugs in lung cells and mice and found that the combinations were very effective against multiple strains of the new coronavirus, including the Delta variant. The team is currently conducting drug tests against the Omiljun strain.

In addition, the study also found that the oral antiviral drug Paxlovid, which was recently authorized by the FDA, can be used in combination with remdesivir or monapiravir to have a synergistic effect on the new crown virus. They plan to conduct human clinical trials of these drug combinations next.