Remdesivir (GS-5734)

Remdesivir is a prodrug form of the antiviral nucleotide analog GS-443902.^1,2,3 Upon entry into cells, remdesivir is metabolized into the intermediate metabolite GS-441524 , which is then further metabolized to the active nucleotide triphosphate GS-443902 that induces RNA chain termination and inhibits viral polymerases.⁴ Remdesivir reduces viral titers in primary human airway epithelial (HAE) cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV) or severe acute respiratory syndrome CoV (SARS-CoV; EC₅₀s = 0.074 and 0.069 ?M, respectively). It reduces infectious virus production in SARS-CoV-2-infected HAE cells (EC₅₀ = 10 nM).⁵ In vivo, remdesivir (25 and 50 mg/kg) reduces lung viral titers and prevents weight loss in a mouse model of SARS-CoV infection.² Remdesivir (25 mg/kg) also reduces lung viral titers and lung hemorrhage and improves pulmonary function in mice infected with a chimeric SARS-CoV encoding the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).⁵ Formulations containing remdesivir have been used in the treatment of COVID-19.
瑞德西韦是一种抗病毒核苷酸类似物GS-443902的前药形式。^1,2,3 进入细胞后，瑞德西韦被代谢成中间代谢物GS-441524，进一步代谢为活性核苷酸三磷酸GS-443902，诱导RNA链终止并抑制病毒聚合酶。⁴ 瑞德西韦可以减少中东呼吸综合症冠状病毒（MERS-CoV）或严重急性呼吸综合症冠状病毒（SARS-CoV）感染的人类气道上皮原代细胞（HAE）中的病毒滴度（EC50分别为0.074和0.069μM）。它可以降低SARS-CoV-2感染的HAE细胞中的传染性病毒产量（EC50 = 10 nM）。⁵在体内，瑞德西韦（25和50 mg/kg）可以减少SARS-CoV感染小鼠的肺病毒滴度，并防止体重下降。² 瑞德西韦（25 mg/kg）还可以减少感染编码SARS-CoV-2 RNA依赖性RNA聚合酶（RdRp）的嵌合SARS-CoV感染小鼠的肺病毒滴度和肺出血，并改善肺功能。⁵ 含瑞德西韦的制剂已用于COVID-19的治疗

1.Agostini, M.L., Andres, E.L., Sims, A.C., et al.Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonucleasemBio9(2)e00221-00218(2018) 2.Sheahan, T.P., Sims, A.C., Graham, R.L., et al.Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronavirusesSci. Transl. Med.9(396)eaal3653(2017) 3.Cox, R.M., Wolf, J.D., Lieber, C.M., et al.Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferretsNat. Commun.12(1)6415(2021) 4.Eastman, R.T., Roth, J.S., Brimacombe, K.R., et al.Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19ACS Cent. Sci.6(5)672-683(2020) 5.Pruijssers, A.J., George, A.S., Sch?fer, A., et al.Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in miceCell Rep.32(3)107940(2020)