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| Targets |
RdRp, RSV,SARS-CoV-2, HCV, COVID-19, LCMV[1][2][3].
EIDD-2749 targets the RNA-dependent RNA polymerase (RdRp) of single-stranded RNA viruses, including RSV and SARS-CoV-2. The compound is a ribonucleoside analog that is incorporated into viral RNA during replication. Incorporation of EIDD-2749 into viral RNA inhibits viral RdRp and induces transcriptional stalling, leading to chain termination and reduced viral replication. The compound's mechanism of action is similar to other nucleoside analog RdRp inhibitors. |
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| ln Vitro |
EIDD-2749 causes RSV and SARS-CoV-2 RdRP to stop the synthesis of phosphodiester bonds later than expected[1]. In disease-relevant, well-differentiated HAE cells, EIDD-2749 is quickly anabolized, metabolically stable, and potently antiviral[1]. Compared to HEp-2 cells, EIDD-2749 has an anti-RSV potency that is approximately 17 times more potent. Despite this, the low cytotoxicity levels (CC50 169 mM) remain unchanged, resulting in a high SI (SI = EC50/CC50) of approximately 1877[1]. EIDD-2749 has an EC50 value between 0.2 and 0.6 M, which suppresses SARS-CoV-2[2]. EIDD-2749 exhibits stability in human plasma, cytotoxicity with a CC50 of 380 μM, and an EC50 of 1.86 μM in the Vero E6 cell line[3].
In vitro studies demonstrate that EIDD-2749 effectively inhibits the replication of RSV and SARS-CoV-2. The compound is a ribonucleoside analog that inhibits viral RdRp. Incorporation of EIDD-2749 into viral RNA induces transcriptional stalling in cell-free assays. EIDD-2749 reduces viral yield in HEp-2 cells infected with RSV. The compound also exhibits activity against HCV and LCMV. No detailed EC50 or IC50 values have been published in the available literature. |
| ln Vivo |
In an RSV infection mouse model, EIDD-2749 (0.2, 1, 5 mg/kg; po; once daily for 4 days) exhibits good oral efficacy in a dose-dependent manner[1]. In comparison to molnupiravir given twice daily in vivo, EIDD-2749 exhibits high efficacy against SARS-CoV-2 infection and can be delivered as a single daily dose[2].
In vivo, orally administered EIDD-2749 reduces lethal infection with pandemic human and highly pathogenic avian influenza viruses. The compound is an orally active RdRp inhibitor that effectively blocks viral replication. EIDD-2749 has been studied for its potential to treat infections caused by RSV and SARS-CoV-2. Its broad-spectrum antiviral activity makes it a promising candidate for further development as an antiviral therapeutic. |
| Enzyme Assay |
The RdRp inhibitory activity of EIDD-2749 can be assessed using cell-free polymerase assays. In a typical assay, purified viral RdRp (from RSV or SARS-CoV-2) is incubated with a RNA template, nucleotide substrates (including radiolabeled or fluorescently labeled nucleotides), and varying concentrations of EIDD-2749 (as the active triphosphate form). The incorporation of nucleotides into the growing RNA chain is measured, and the IC50 is calculated. Transcriptional stalling can be detected by analyzing the length of RNA products.
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| Cell Assay |
The antiviral activity of EIDD-2749 is assessed using virus-infected cell lines. In a typical assay, HEp-2 cells (for RSV) or Vero E6 cells (for SARS-CoV-2) are infected with virus and treated with varying concentrations of EIDD-2749. Viral replication is measured by quantifying viral RNA using qRT-PCR or by plaque assays. Cytotoxicity is assessed in uninfected cells using MTT assays. The compound's antiviral activity against HCV and LCMV can be assessed using appropriate cell culture models.
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| Animal Protocol |
Animal/Disease Models: Balb/cJ mice (RSV infection model )[1].
Doses: 0.2, 1, 5 mg/kg Route of Administration: Oral administration; single daily for 4 days Experimental Results: Resulted in a statistically significant reduction in lung virus load. EIDD-2749 has been evaluated in animal models of viral infection. In studies of influenza virus infection, orally administered EIDD-2749 reduced lethal infection with pandemic human and highly pathogenic avian influenza viruses. The compound has also been studied in animal models of RSV and SARS-CoV-2 infection. Further studies would be needed to fully characterize its efficacy in various viral infection models. |
| ADME/Pharmacokinetics |
EIDD-2749 is orally active, indicating favorable oral bioavailability. The compound has a molecular weight of 262.19 and a molecular formula of C9H11FN2O6. It is soluble in DMF (20 mg/mL), DMSO (10 mg/mL), and PBS (pH 7.2, 10 mg/mL). The compound has a maximum absorbance at 261 nm. It is typically stored at -20°C and is stable at room temperature for a few days during shipping.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published for EIDD-2749. As a nucleoside analog RdRp inhibitor, the compound may have off-target effects on host polymerases. However, its selectivity for viral RdRp over host polymerases contributes to its antiviral activity and safety profile. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound has been studied in preclinical models of viral infection and has shown a favorable safety profile.
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| References |
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| Additional Infomation |
EIDD-2749 (4'-Fluorouridine; 4'-FlU; CAS# 1613589-24-4) is an orally active ribonucleoside analog and RdRp inhibitor that effectively blocks the replication of RSV and SARS-CoV-2. It also exhibits activity against HCV and LCMV. Incorporation of EIDD-2749 into viral RNA inhibits viral RdRp and induces transcriptional stalling. The compound reduces viral yield in HEp-2 cells infected with RSV and reduces lethal influenza virus infection in vivo. The molecular formula is C9H11FN2O6 and molecular weight is 262.19.
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| Molecular Formula |
C9H11FN2O6
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|---|---|
| Molecular Weight |
262.19
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| Exact Mass |
262.06
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| CAS # |
1613589-24-4
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| PubChem CID |
54260440
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.77±0.1 g/cm3(Predicted)
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| LogP |
-2
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
416
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1=CN(C(=O)NC1=O)[C@H]2[C@@H]([C@@H]([C@](O2)(CO)F)O)O
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| InChi Key |
RDCYLPRXPILMRP-JVZYCSMKSA-N
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| InChi Code |
InChI=1S/C9H11FN2O6/c10-9(3-13)6(16)5(15)7(18-9)12-2-1-4(14)11-8(12)17/h1-2,5-7,13,15-16H,3H2,(H,11,14,17)/t5-,6+,7-,9-/m1/s1
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| Chemical Name |
1-[(2R,3R,4S,5S)-5-fluoro-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : 62.5 mg/mL (238.38 mM)
DMSO : 25 mg/mL (95.35 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 25 mg/mL (95.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 250.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (9.54 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8140 mL | 19.0701 mL | 38.1403 mL | |
| 5 mM | 0.7628 mL | 3.8140 mL | 7.6281 mL | |
| 10 mM | 0.3814 mL | 1.9070 mL | 3.8140 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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