TDI-015051 

TDI-015051 is a highly selective, orally active antiviral agent that targets the coronavirus NSP14 guanine-N7 methyltransferase. TDI-015051 binds to substrates in a non-competitive manner and forms a stable ternary complex, precisely blocking the capping and methylation processes of viral mRNA. TDI-015051 potently inhibits a variety of coronaviruses (including SARS-CoV-2 and MERS). By impairing viral replication and translation and inducing a moderate type I interferon-mediated immune response, it significantly reduces pulmonary viral load and exhibits a synergistic effect with Nirmatrelvir (HY-138687). In addition, TDI-015051 does not inhibit non-coronavirus methyltransferases, and the drug-resistant mutations it induces impair viral fitness, demonstrating excellent antiviral properties and safety. TDI-015051 can be used for research on COVID-19 and the replication mechanism of coronaviruses^[1].The IC₅₀ values of TDI-015051 against SARS-CoV-2, α-hCoV-NL63, α-hCoV-229E, β-hCoV-MERS are 0.15 nM, 1.7 nM, 2.6 nM and 3.6 nM, respectively, and the K_a value against SARS-CoV-2 is 0.061 nM^[1].

TDI-015051 (dose-response format) potently inhibits SARS-CoV-2 NSP14 guanine-N7 methyltransferase activity in a biochemical assay with an IC₅₀ ≤ 0.15 nM^[1].
TDI-015051 inhibits SARS-CoV-2 infection in Huh-7.5 cells with an EC₅₀ of 11.4 nM, and this activity is potentiated to an EC₅₀ of 0.8 nM by co-treatment with 5 μM DZNeP, with no cytotoxicity at concentrations ≤ 3 μM^[1].
TDI-015051 (0.1-16 nM; 4 days post-infection) completely inhibits SARS-CoV-2 replication in human primary small airway epithelial cells at concentrations ≥ 4 nM^[1].
TDI-015051 (dose-response format; 1 h pre-treatment; 24 h, 48 h, 72 h post-infection evaluation) inhibits SARS-CoV-2 infection in Vero E6 cells with EC₅₀ values of 99.5 nM, 71.1 nM, and 52.4 nM at 24 h, 48 h, and 72 h post-infection, respectively, following 1 h pre-treatment^[1].
TDI-015051 (dose-response format) inhibits infection by multiple human coronaviruses in cell-based assays, with EC₅₀ values of 0.12 μM for α-hCoV-NL63, 3.7 μM for α-hCoV-229E, and 6.5 μM for β-hCoV-MERS, with no detectable cytotoxicity at the tested concentrations^[1].
TDI-015051 (dose-response format) does not inhibit SARS-CoV-2 NSP16-NSP10, human RNMT-RAM, or Zika virus NS5 methyltransferases, demonstrating selective activity against coronavirus NSP14^[1].
TDI-015051 (1 μM; 1 h pre-treatment, 24 h infection) treatment of SARS-CoV-2-infected A549-ACE2-TMPRSS2 cells induces a weak type I interferon-mediated immune response via increased interferon-stimulated gene expression^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TDI-015051 (150-500 mg/kg; p.o.; twice daily; 4 days), administered starting 12 h before infection in mice, reduces the SARS-CoV-2 lung viral titer in K18-hACE2 mice by approximately 2 orders of magnitude, with efficacy comparable to that of Nirmatrelvir (HY-138687)^[1].
Treatment with TDI-015051 (500 mg/kg; p.o.; twice daily; 4 days) initiated 1 h prior to infection in mice reduces the SARS-CoV-2 lung viral titer in K18-hACE2 mice by one order of magnitude, with efficacy comparable to that of Nirmatrelvir (HY-138687).

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

471.50

C₂₂H₂₂FN₅O₄S

3052313-73-9

O=S(N(CC1)CC2=C1NN=C2)(C3=C(C)N(C)C(C(NCC4=C(F)C=CC5=C4C=CO5)=O)=C3)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Meyer C, et al. Small-molecule inhibition of SARS-CoV-2 NSP14 RNA cap methyltransferase. Nature. 2025;637(8048):1178-1185.  [Content Brief]