Remdesivir (GS-5734)
(Synonyms: 瑞德西韦; GS-5734) 目录号 : GC32223
Remdesivir (GS-5734)是一种高效抗病毒药物，对SARS-CoV-2病毒及相关α、β、γ和δ变异株的EC50值分别为3.3μM、4.7μM、32μM、3.7μM和9.2μM。
Cas No.:1809249-37-3
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Remdesivir (GS-5734) is a highly potent antiviral drug, with the EC50 values of 3.3μM, 4.7μM, 32μM, 3.7μM and 9.2μM for SARS-CoV-2 virus and the related variants, alpha, beta, gamma, and delta, respectively[1]. Remdesivir, which is integrated into nascent viral RNA strands and causes premature termination of transcription, has been shown to treat various RNA virus infections such as Ebola virus (EBOV) in cell cultures, mice, and non-human primates (NHP) models[2].
In vitro, Remdesivir treatment for 72 hours inhibited EBOV replication in multiple relevant human cell types, including primary macrophages and human endothelial cells, with EC50 values of 0.06-0.14μM[3]. Remdesivir significantly inhibited Middle East respiratory syndrome coronavirus (MERS-CoV) replication in 2B4 cells after 48 hours of treatment, with an IC50 value of 0.025μM[4]. Pre-treatment of HeLa cells with 100μM Remdesivir for 2 hours can effectively inhibit the replication of EV71 virus in the cells, without affecting cell viability[5].
In vivo, Remdesivir treatment (10mg/kg) through intravenous injection once daily for 12 days can protect African green monkeys from fatal Nipah virus infection[6]. In the Ces1c−/− hDPP4 mouse model, subcutaneous injection of Remdesivir (25mg/kg) one day before infection with MERS-CoV virus could reduce the characteristics of acute lung injury (ALI) caused by MERS-CoV virus, inhibit the replication of MERS-CoV virus, and improve lung function[7]. Intravenous administration of 5mg/kg Remdesivir to rhesus monkeys 24h before MERS-CoV inoculation completely prevented the clinical disease induced by MERS-CoV, effectively inhibited the replication of MERS-CoV in respiratory tissues, and prevented the formation of lung lesions[8].
References:
[1] Hu H, Mady Traore M D, Li R, et al. Optimization of the prodrug moiety of remdesivir to improve lung exposure/selectivity and enhance anti-SARS-CoV-2 activity[J]. Journal of Medicinal Chemistry, 2022, 65(18): 12044-12054.
[2] Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro[J]. Cell research, 2020, 30(3): 269-271.
[3] Warren T K, Jordan R, Lo M K, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys[J]. Nature, 2016, 531(7594): 381-385.
[4] Sheahan T P, Sims A C, Graham R L, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses[J]. Science translational medicine, 2017, 9(396): eaal3653.
[5] Ye W, Yao M, Dong Y, et al. Remdesivir (GS-5734) impedes enterovirus replication through viral RNA synthesis inhibition[J]. Frontiers in microbiology, 2020, 11: 1105.
[6] Lo M K, Feldmann F, Gary J M, et al. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge[J]. Science translational medicine, 2019, 11(494): eaau9242.
[7] Sheahan T P, Sims A C, Leist S R, et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV[J]. Nature communications, 2020, 11(1): 222.
[8] De Wit E, Feldmann F, Cronin J, et al. Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection[J]. Proceedings of the National Academy of Sciences, 2020, 117(12): 6771-6776.
Remdesivir (GS-5734)是一种高效抗病毒药物，对SARS-CoV-2病毒及相关α、β、γ和δ变异株的EC50值分别为3.3μM、4.7μM、32μM、3.7μM和9.2μM[1]。Remdesivir被整合到新生病毒RNA链中并导致转录提前终止，已被证明可以治疗细胞培养物、小鼠和非人灵长类动物（NHP）模型中的各种RNA病毒感染，如埃博拉病毒(EBOV)[2]。
在体外，Remdesivir (GS-5734)处理72小时可抑制EBOV在人类原代巨噬细胞、内皮细胞等多种细胞中的复制，EC50值为0.06-0.14μM[3]。Remdesivir处理48小时后，对2B4细胞中中东呼吸综合征冠状病毒（MERS-CoV）的IC50值为0.025μM[4]。100μM浓度的Remdesivir预处理HeLa细胞2小时能有效抑制EV71病毒复制，且不影响细胞活性[5]。
在体内，非洲绿猴每日静脉注射10mg/kg剂量的Remdesivir (GS-5734)，连续12天，可完全预防尼帕病毒致死性感染[6]。在Ces1c−/− hDPP4小鼠模型感染MERS-CoV前1天皮下注射25mg/kg剂量的Remdesivir能减轻由MERS-CoV引起的急性肺损伤（ALI）特征、抑制MERS-CoV复制并改善肺功能[7]。恒河猴在MERS-CoV感染的前24小时静脉注射5mg/kg剂量的Remdesivir，可完全阻断MERS-CoV感染的临床症状，有效抑制MERS-CoV在呼吸组织的复制并预防肺部病变形成[8]。
| Cell experiment [1]: | |
Cell lines | Human lung epithelial 2B4 cells |
Preparation Method | The human lung epithelial 2B4 cell was cultured in the Doudou Modified Eiger Medium, 20% fetal bovine serum, and 1× antibiotics and antifungal agents. 5×104 cells were inoculated per well 24 hours later, and fresh medium was added. Three replicates were prepared, and MERS-nLUC (MOI 0.08) diluted with growth medium was used to infect the cells for 1 hour. Then the virus was removed, the culture was washed once, and fresh medium containing Remdesivir (GS-5734) diluent (0.001, 0.01, 0.1, 1, 10, 100μM) or the vehicle was added. DMSO (0.05%) remained unchanged under all conditions. At 48 hours post-infection (hpi), viral replication was measured by nLUC assay, cytotoxicity was measured by CellTiter-Glo assay, and readings were taken on the SpectraMax plate reader. The IC50 value was defined in GraphPad Prism 7 software as the concentration at which viral replication decreased by 50% compared to UV-treated MERS-nLUC (100% inhibition) and only using the vector (0% inhibition). |
Reaction Conditions | 0.001, 0.01, 0.1, 1, 10, 100μM; 48h |
Applications | Remdesivir (GS-5734) significantly inhibited MERS-CoV replication in 2B4 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | African green monkeys |
Preparation Method | Eight adult African green monkeys were randomly divided into two groups (2 males and 2 females each) and were intranasally injected with 105 50% tissue culture infective dose (TCID50) (0.5ml per nostril) and 105 TCID50 (4ml) of the Bangladesh Nipah virus through the trachea. One group of animals received the vehicle solution of Remdesivir (10mg/kg) [12% sulfobutylether-β-cyclodextrin aqueous solution (pH 3.5)], the other group received the same volume (2ml/kg) of the vehicle solution. Remdesivir (GS-5734) and vehicle solution were administered by slow intravenous infusion (approximately 5 minutes for the total dose), alternately through the left or right cranial vein and jugular vein. The treatment was given once daily for 12 days. After vaccination with the Nipah virus, the animals' disease symptoms were monitored, and clinical scores were assessed according to the approved scoring table by the Institutional Animal Care and Use Committee (IACUC). Clinical examinations were conducted at 0, 1, 3, 5, 8, 15, 19, 23, 28, 35, 42, 50, 63, and 92 days after infection. On the examination days, clinical parameters such as body weight, respiratory rate, and blood oxygen saturation (SPO2) were collected, as well as blood samples and oral and nasal swabs. Autopsies were performed after the animals died of euthanasia. |
Dosage form | 10mg/kg/day for 12 days; i.v. |
Applications | Remdesivir (GS-5734) treatment protected African green monkeys from lethal Nipah virus Bangladesh disease and alleviated respiratory symptoms. |
References: | |
| Cas No. | 1809249-37-3 | SDF | |
| 别名 | 瑞德西韦; GS-5734 | ||
| 化学名 | (2S)-2-ethylbutyl 2-(((((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate | ||
| Canonical SMILES | N#C[C@@]1(C2=CC=C3N2N=CN=C3N)O[C@H](COP(OC4=CC=CC=C4)(N[C@@H](C)C(OCC(CC)CC)=O)=O)[C@@H](O)[C@H]1O | ||
| 分子式 | C27H35N6O8P | 分子量 | 602.58 |
| 溶解度 | DMSO : ≥ 125 mg/mL (207.44 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6595 mL | 8.2977 mL | 16.5953 mL |
| 5 mM | 0.3319 mL | 1.6595 mL | 3.3191 mL |
| 10 mM | 0.166 mL | 0.8298 mL | 1.6595 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet