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T-1105 (T1105), an analog of T-705 (favipiravir), is a novel and potent broad-spectrum antiviral inhibitor that inhibits the polymerases of RNA viruses after being converted to the actiive form: ribonucleoside triphosphate (RTP) metabolite. T-1105 has a broad spectrum of antiviral activity against various RNA viruses, including Zika virus (ZIKV), influenza virus, arenaviruses, bunyaviruses, West Nile virus (WNV), yellow fever virus (YFV), and foot-and-mouth disease virus (FMDV).
| Targets |
parainfluenza-3 virus（EC50= 17 μM）;Punta Toro virus（EC50= 24 μM）;ZIKV strain SZ01（EC50= 97.5 μM）
The literature indicates that T-1105, as a pyrazinecarboxamide derivative related to T-705 (favipiravir), is presumed to act as a nucleotide analog and inhibit viral RNA-dependent RNA polymerase. Specific inhibition constants (e.g., Ki) for T-1105 against this enzyme are not provided in this text [2]. |
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| ln Vitro |
Zika virus (ZIKV), influenza virus, arenaviruses, bunyaviruses, West Nile virus (WNV), yellow fever virus (YFV), foot-and-mouth disease virus (FMDV), and other RNA viruses are all susceptible to T-1105's antiviral activity[1][2].
T-1105 exhibits strong anti-RNA virus activity against the parainfluenza-3 virus and the Punta Toro virus in MDCK cells, with EC50 values of 17 μM and 24 μM, respectively[3]. One possible inhibitor of the Zika virus's replication is T-1105[4]. T-1105 does not affect cell viability at concentrations of 0–3 μM, but it can inhibit SFTSV replication in Vero cells with an IC50 of 49 μM[5]. The anti-FMDV (foot-and-mouth disease virus) activity of T-1105 was assessed using a plaque reduction assay with the O/PN/2000 strain. It demonstrated potent antiviral activity with an EC50 value of 12 μM [2]. T-1105 also showed activity against bovine viral diarrhea virus (BVDV), a flavivirus, in MDBK cells. In a yield reduction assay, it reduced BVDV replication with an EC50 value of 34 μM [2]. |
| ln Vivo |
T-1105 (200 mg/kg, twice day for 6 days) effectively prevents the virus from replicating in infected pigs[6].
The in vivo efficacy of T-1105 was evaluated in pigs infected with foot-and-mouth disease virus (FMDV). Four pigs were administered T-1105 at a dose of 200 mg/kg twice daily for 6 days, starting 1 hour prior to virus inoculation. Throughout the experiment, the treated pigs showed no clinical signs of FMD (such as fever, foot vesicles, or lameness), whereas control animals displayed typical symptoms. Viremia in treated pigs was effectively reduced to below detectable levels, and the increase in anti-FMD antibody titers was suppressed, indicating effective inhibition of virus replication. Importantly, the virus was not detected in nasal swabs from T-1105-treated animals [2]. |
| Cell Assay |
Cell Line: Vero cells
Concentration: 0-3 μM Incubation Time: 4 h Result: Did not affect cell viability in the test range (0-3 μM). Plaque Reduction Assay (for FMDV): The anti-FMDV activity of T-1105 was evaluated in cell culture using a plaque reduction assay. Cells were infected with the FMDV O/PN/2000 strain and treated with varying concentrations of the compound. The EC50, the concentration required to reduce plaque formation by 50%, was determined to be 12 μM [2]. Yield Reduction Assay (for BVDV): The activity of T-1105 against bovine viral diarrhea virus (BVDV) was tested in MDBK cells using a yield reduction assay. Cells were infected with BVDV and treated with the compound. The reduction in virus yield was measured, and the EC50 was calculated to be 34 μM [2]. |
| Animal Protocol |
Animal Model: Pigs[6]
Dosage: 200 mg/kg Administration: Oral, 200 mg/kg, twice daily for 6 days Result: decreased viremia and elevated anti-FMD antibody titers, but no clinical indications of FMD were seen. Efficacy Study in FMDV-Infected Pigs:** Four pigs were treated with T-1105 to evaluate its effect on foot-and-mouth disease virus infection. The compound was administered through feed at a dose of 200 mg/kg, twice daily, for a total of 6 days. Treatment began 1 hour prior to inoculation with FMDV. Control animals were not treated. Animals were monitored for clinical signs of disease (fever, vesicular lesions, lameness). Viremia and anti-FMDV antibody titers were measured from blood samples, and virus secretion was monitored via nasal swabs [2]. Efficacy Study in FMDV-Infected Pigs: Four pigs were treated with T-1105 to evaluate its effect on foot-and-mouth disease virus infection. The compound was administered through feed at a dose of 200 mg/kg, twice daily, for a total of 6 days. Treatment began 1 hour prior to inoculation with FMDV. Control animals were not treated. Animals were monitored for clinical signs of disease (fever, vesicular lesions, lameness). Viremia and anti-FMDV antibody titers were measured from blood samples, and virus secretion was monitored via nasal swabs [2]. |
| References |
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| Additional Infomation |
Background: T-1105 is a pyrazinecarboxamide derivative discovered and synthesized by Toyama Chemical Co., Ltd. It was identified as a lead compound through screening for antiviral activity against influenza virus. It is structurally related to T-705 (favipiravir) and T-1106 [2].
Mechanism of Action (Presumed): As a member of the pyrazinecarboxamide series, T-1105 is believed to share a similar mechanism of action with T-705. It is likely converted by host cellular enzymes to a ribofuranosyltriphosphate metabolite, which then selectively inhibits the viral RNA-dependent RNA polymerase [2]. Efficacy in FMDV: The study highlights the potential of T-1105 as a powerful tool to control foot-and-mouth disease outbreaks in pigs. Its ability to be administered via feed allows for easy treatment of large numbers of animals. The suppression of clinical signs, viremia, and, most importantly, virus secretion (as evidenced by negative nasal swabs) suggests it could effectively reduce virus spread [2]. Activity Against Other Viruses: In addition to FMDV, T-1105 has shown in vitro activity against bovine viral diarrhea virus (BVDV), a surrogate model for hepatitis C virus (HCV) [2]. |
| Molecular Formula |
C5H5N3O2
|
|---|---|
| Molecular Weight |
139.114
|
| Exact Mass |
139.038
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| Elemental Analysis |
C, 43.17; H, 3.62; N, 30.21; O, 23.00
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| CAS # |
55321-99-8
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| Related CAS # |
Favipiravir;259793-96-9
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| PubChem CID |
294642
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| Appearance |
Off-white to light brown solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
640.8±55.0 °C at 760 mmHg
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| Melting Point |
ca 270℃
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| Flash Point |
341.3±31.5 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.634
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| LogP |
0.32
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
10
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| Complexity |
241
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=NC=CN=C1O)N
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| InChi Key |
SZPBAPFUXAADQV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C5H5N3O2/c6-4(9)3-5(10)8-2-1-7-3/h1-2H,(H2,6,9)(H,8,10)
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| Chemical Name |
3-oxo-3,4-dihydropyrazine-2-carboxamide
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| Synonyms |
T 1105; T1105.
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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) |
DMSO : ~25 mg/mL (~179.71 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (17.97 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (17.97 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. 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (17.97 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 7.1886 mL | 35.9428 mL | 71.8856 mL | |
| 5 mM | 1.4377 mL | 7.1886 mL | 14.3771 mL | |
| 10 mM | 0.7189 mL | 3.5943 mL | 7.1886 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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