In Vitro Synergistic Antiviral Effects of β-D-N4-hydroxycytidine and Teriflunomide in Combination against a Broad Range of RNA Viruses.

Publication date: Jul 01, 2025

Emerging and important endemic viral diseases without effective antiviral are important public health threat. An effective broad-spectrum antiviral can be a pivotal tool to mitigate future epidemics and provide a solution for endemic viral diseases. Molnupiravir, a pyrimidine analog, is known for the COVID-19 treatment. It has been shown to inhibit a broad range of RNA viruses. Inhibition of de novo pyrimidine synthesis by teriflunomide, a dihydroorotate dehydrogenase inhibitor, also showed potent antiviral activity against various RNA viruses. Mechanistically, pyrimidine synthesis inhibition should enhance the activity of molnupiravir as it reduces competition of native nucleotides to incorporate into nascent viral RNA. Molnupiravir and teriflunomide combination has been recently shown to have synergistic effect against SARS-CoV-2. Here we show that the combination of β-D-N4-hydroxycytidine, the active form of molnupiravir, and teriflunomide also showed synergistic activity against many RNA viruses. This combination may offer an effective antiviral regimen not only for future emerging viral diseases but also existing important viral diseases.

Concepts Keywords
Broad Animals
Competition antiviral
Covid Antiviral Agents
Hydroxycytidine Antiviral Agents
Viruses broad‐spectrum
Crotonates
Crotonates
Cytidine
Cytidine
Drug Synergism
Humans
Hydroxybutyrates
Hydroxybutyrates
Hydroxylamines
Hydroxylamines
molnupiravir
N(4)-hydroxycytidine
Nitriles
Nitriles
repurposing drugs
RNA Viruses
RNA viruses
SARS-CoV-2
synergistic effects
teriflunomide
Toluidines
Toluidines
Vero Cells

Semantics

Type Source Name
drug DRUGBANK Teriflunomide
disease MESH viral diseases
disease MESH COVID-19
drug DRUGBANK Cytidine

Original Article

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