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]。