Human pyrimidine nucleotide biosynthesis as a target for antiviral chemotherapy
Highlights•Human pyrimidine nucleotide biosynthesis has been targeted for the treatment of
many diseases.•Chemotherapy combining DHODH and UCK inhibitors can be a broad-
spectrum antiviral.•Targeting the host cell, such an antiviral therapy could mitigate resistant
viruses.The development of broad-spectrum, host-acting antiviral therapies remains an
important but elusive goal in anti-infective drug discovery. To replicate efficiently, viruses not
only depend on their hosts for an adequate supply of pyrimidine nucleotides, but also up …
many diseases.•Chemotherapy combining DHODH and UCK inhibitors can be a broad-
spectrum antiviral.•Targeting the host cell, such an antiviral therapy could mitigate resistant
viruses.The development of broad-spectrum, host-acting antiviral therapies remains an
important but elusive goal in anti-infective drug discovery. To replicate efficiently, viruses not
only depend on their hosts for an adequate supply of pyrimidine nucleotides, but also up …
Highlights
- Human pyrimidine nucleotide biosynthesis has been targeted for the treatment of many diseases.
- Chemotherapy combining DHODH and UCK inhibitors can be a broad-spectrum antiviral.
- Targeting the host cell, such an antiviral therapy could mitigate resistant viruses.
The development of broad-spectrum, host-acting antiviral therapies remains an important but elusive goal in anti-infective drug discovery. To replicate efficiently, viruses not only depend on their hosts for an adequate supply of pyrimidine nucleotides, but also up-regulate pyrimidine nucleotide biosynthesis in infected cells. In this review, we outline our understanding of mammalian de novo and salvage metabolic pathways for pyrimidine nucleotide biosynthesis. The available spectrum of experimental and FDA-approved drugs that modulate individual steps in these metabolic pathways is also summarized. The logic of a host-acting combination antiviral therapy comprised of inhibitors of dihydroorotate dehydrogenase and uridine/cytidine kinase is discussed.
Elsevier
