venezuelan

EIDD-1931 (Beta-d-N4-hydroxycytidine) 是一种核苷类抗病毒试剂 ，可抑制丙型肝炎病毒、基孔肯亚病毒和委内瑞拉马脑炎病毒的复制活性。

nsP2 Protease-IN-1 是一种针对 Chikungunya (CHIKV) 病毒nsP2半胱氨酸蛋白酶的高效不可逆共价抑制剂，IC50为60 nM。该化合物具有出色的抗阿尔法病毒活性，能够有效抑制 CHIKV 和 VEEV 的病毒复制，其 EC50 值分别为0.01 µM 和 0.3 µM。

AAK1-IN-6 (化合物 23) 是一种针对 AP-2 相关蛋白激酶 1 (AAK1, IC50= 12 nM) 的抑制剂，对登革病毒 (DNEV2, EC50= 0.24 μM) 和委内瑞拉马脑炎病毒 (VEEV, EC50= 0.30 μM) 展现出抗病毒活性。AAK1-IN-6 适用于抗病毒研究。

ML-336 是一种喹唑啉酮类的委内瑞拉马脑炎病毒 (VEEV) 抑制剂，其VEEV TC-83 CPE(IC50:32 nM)、VEEV V3526 CPE(IC50:20 nM)、VEEV 野生型 CPE (IC50:42 nM)，有效抑制 VEEV 诱导的三种病毒株 (V3526、TC-83和野生型) 细胞病变效应。

NHC-diphosphate is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a diphosphate form[1]. NHC is a pyrimidine ribonucleoside and behaves as a potent anti-virus agent. NHC effectively inhibits the replication of venezuelan equine encephalitis virus (VEEV), Chikungunya virus (CHIKV) and hepatitis C virus (HCV)[1]. Huh-7 cells are incubated with (10-50 μM; 4 h) NHC or a McGuigan phosphoramidate prodrug of NHC.Intracellular levels of the parental compounds and phosphorylated metabolites are measured using LC-MS MS. Small amounts of NHC-monophosphate (MP) and NHC-diphosphate can be observed, while NHC-triphosphate remains the most abundant metabolite.[1].

STING agonist C11 is an agonist of the stimulator of interferon genes (STING) pathway.1 It induces secretion of type I IFN from THF and MM6 cells when used at a concentration of 50 μM. STING agonist C11 induces phosphorylation of IFN regulatory factor 3 (IRF3) and increases expression of IFIT1 and viperin, but not IL-1β, IL-6, or IL-8 in THF cells in a STING-dependent manner. It reduces viral titers of chikungunya, Venezuelan equine encephalitis, o'nyong-nyong, Mayaro, and Ross River viruses grown in THF cells (EC90s = 16.44, 16.7, 18.84, 25.19, and 22.57 μM, respectively), an effect that is dependent on the presence of STING and the IFN-α β receptor (IFNAR).References1. Gall, B., Pryke, K., Abraham, J., et al. Emerging alphaviruses are sensitive to cellular states induced by a novel small-molecule agonist of the STING pathway. J. Virol. 92(6), e01913-01917 (2018). STING agonist C11 is an agonist of the stimulator of interferon genes (STING) pathway.1 It induces secretion of type I IFN from THF and MM6 cells when used at a concentration of 50 μM. STING agonist C11 induces phosphorylation of IFN regulatory factor 3 (IRF3) and increases expression of IFIT1 and viperin, but not IL-1β, IL-6, or IL-8 in THF cells in a STING-dependent manner. It reduces viral titers of chikungunya, Venezuelan equine encephalitis, o'nyong-nyong, Mayaro, and Ross River viruses grown in THF cells (EC90s = 16.44, 16.7, 18.84, 25.19, and 22.57 μM, respectively), an effect that is dependent on the presence of STING and the IFN-α β receptor (IFNAR). References1. Gall, B., Pryke, K., Abraham, J., et al. Emerging alphaviruses are sensitive to cellular states induced by a novel small-molecule agonist of the STING pathway. J. Virol. 92(6), e01913-01917 (2018).

Encephalitic alphavirus-IN-1 能够抑制委内瑞拉马脑炎病毒 (VEEV) (EC50: 0.24 μM)和东部马脑炎病毒 (EEEV) (EC50: 0.16 μM)的活性。Encephalitic alphavirus-IN-1 没有明显的细胞毒性，而且表现出较强的小鼠血浆稳定性。