PYRIMIDINE BIOSYNTHESIS INHIBITORS ALONG WITH NUCLEOSIDE ANALOGUES TOGETHER TO INHIBIT SARS-CoV-2

Edited by, JASPER VICTORIA

The viruses need high levels of Nucleoside Triphosphates (NTPs)  and hence depend on Nucleoside biosynthesis during growth and viral replication.

Nucleoside analogs were mis-incorporated into the host cells during viral replication instead of the RNA-dependent RNA polymerase which hence lead to chain termination, resulting in inhibition of viral replication.

Remdesvir and Molnupiravir are drugs showing similar inhibitory action at various parts of the life cycle of the virus. Certain antimetabolites such as Tubercidin, Thioguanin and 6-Mercaptopurine used as anticancer drugs were also examined for immunosuppressive property.

The researchers hence found out that it is possible to inhibit the viral replication by blocking the purine and pyrimidine synthesis, i.e. nucleoside biogenesis. They found out the synergism between Brequinar / BAY-2402234,  a dihydro-orotate dehydrogenase inhibitor and the nucleoside analogues such as molnupiravir.

They took on the study in a mouse-model. The researchers, therefore find that the combination of nucleoside inhibitors and  dihydro-orotate inhibitors to be beneficial in covid-19, inhibiting the SARS- CoV-2 replication.