What drugs are effective against COVID-19?

Scientists from the University of Pennsylvania have identified a combination of antiviral drugs effective in the treatment of coronavirus infection COVID-19.

The combined use of pyrimidine biosynthesis inhibitors with nucleoside analogues, such as remdesivir and molnupiravir, already approved by the FDA, suppresses infection caused by new strains of SARS-CoV-2 coronavirus, Nature reported.

According to Lenta.ru, nucleoside analogs are inserted using the viral RNA-dependent RNA polymerase (RdRp) into the growing RNA chain, which leads to blocking of virus replication. A promising approach is one in which drugs target the pathways of host cell synthesis of the nucleosides required for virus propagation. In the new work, the scientists screened 18,000 candidate antiviral drugs using the Calu-3 human epithelial cell line.

Calu-3 are lung cancer tumor cells, so the researchers used them as a model of respiratory tissues infected with coronavirus.

Scientists have identified 122 drugs that have demonstrated antiviral activity and high selectivity against coronavirus, including 16 nucleoside analogs, including remdesivir and molnupiravir. A group of nucleoside biosynthesis inhibitors was identified among these drugs, including the experimental drug brekinar (Brequinar, DuP-785), which is undergoing clinical trials as an anti-COVID-19 drug and as a component of combination therapy against certain types of cancer. Brekinar blocks the synthesis of pyrimidines, which are a component of pyrimidine nucleosides.

The researchers showed that the combination of remdesivir and molnupiravir leads to an additive effect, that is, their combined action is the sum of their actions separately.

The combination of nucleoside analogues with brekinar created a much more powerful synergistic effect, resulting in a significant reduction in coronavirus titer regardless of the strain.

The scientists also tested the drugs in mice and showed that combining brekinar with molnupiravir protected the lungs of rodents from infection and inflammation.