IrsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona (UAB), Badalona, Spain
Antimicrob Agents Chemother. 2021 Mar 18;65(4). doi: 10.1128/AAC.00200-21.
Finding antivirals to reduce coronavirus disease 2019 (COVID-19) morbidity and mortality has been challenging. Large randomized clinical trials that aimed to test four repurposed drugs, hydroxychloroquine, lopinavir-ritonavir, interferon beta 1a, and remdesivir, have shown that these compounds lack an impact on the COVID-19 course. Although the phase III COVID-19 vaccine trial results are encouraging, the search for effective COVID-19 therapeutics should not stop. Recently, plitidepsin (aplidin) demonstrated highly effective preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its antiviral activity was 27.5-fold more potent than that of remdesivir (K. M. White, R. Rosales, S. Yildiz, T. Kehrer, et al., Science, 2021, https://science.sciencemag.org/content/early/2021/01/22/science.abf4058). Plitidepsin, a repurposed drug developed for the treatment of multiple myeloma, targets the host translation cofactor eEF1A. Plitidepsin has shown efficacy in animal models and phase I/II human trials. Although plitidepsin is administered intravenously and its toxicity profile remains to be fully characterized, this compound may be a promising alternative COVID-19 therapeutic.
寻找能够降低 2019 冠状病毒病（COVID-19）发病率和死亡率的抗病毒药物一直具有挑战性。四项已上市药物再利用的大型随机临床试验，包括羟氯喹、洛匹那韦-利托那韦、干扰素-β1a 和瑞德西韦，均表明这些化合物对 COVID-19 病程没有影响。尽管 III 期 COVID-19 疫苗试验结果令人鼓舞，但对有效 COVID-19 疗法的探索不应停止。最近，plitidepsin（阿普立啶）在对抗严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）方面显示出高度有效的临床前活性。其抗病毒活性比瑞德西韦强 27.5 倍（K.M.White、R.Rosales、S.Yildiz、T.Kehrer 等人，Science，2021，https://science.sciencemag.org/content/early/2021/01/22/science.abf4058）。Plitidepsin 是一种为治疗多发性骨髓瘤而开发的再利用药物，其作用靶点是宿主翻译辅助因子 eEF1A。Plitidepsin 在动物模型和 I/II 期临床试验中均显示出疗效。尽管 plitidepsin 是静脉注射给药，其毒性特征仍有待全面描述，但该化合物可能是一种有前途的 COVID-19 治疗替代药物。
