EIDD-1931 (Beta-d-N4-hydroxycytidine, β-d-N4-hydroxycytidine, NHC)是EIDD-2801的活性代谢产物,它是一种很有前途的 COVID-19 抑制剂。 EIDD-1931(NHC)对 SARS-CoV-2、MERS-CoV、SARS-CoV 和 related zoonotic group 2b或2c Bat-CoVs,对应的平均IC50值为0.15 μM,并且对带有对核苷类似物抑制剂remdesivir耐药性突变的冠状病毒的效力增强。
Beta-d-N4-hydroxycytidine is an anti-VEEV (venezuelan equine encephalitis virus) agent with
EC
50
,
EC
90
, and
EC
99
are 0.426, 1.036, and 2.5 μM, respectively.Beta-d-N4-hydroxycytidine inhibits CHIKV replicon activity and the 50% effective concentration (EC
50
) s 0.8 μM in the Huh-7–CHIKV replicon cell line. Similar results is presented with the replicon in BHK-21 cells (EC
50
=1.8 μM).
NHC has no cytotoxicity for NHC in the Huh-7 cell culture system until up to 100 μM using MTT assays. The 50% cytotoxic concentration (CCsub>50) values for NHC are determined to be 30.6 μM, 7.7 μM, and 2.5 μM in peripheral blood mononuclear (PBM), Vero, and CEM cells, respectively.NHC behaves as a pyrimidine analog, NHC-mediated inhibition of the CHIKV replicon can be abrogated by the addition of exogenous nucleosides, such as pyrimidines C and U, but dA, dC, dG, dU, or T has no impact on the replicon. Pyrimidines A and G contributes to replicon inhibition both in the presence and in the absence of NHC.