普利替德辛在需要住院治疗的成年新冠肺炎患者中具有良好的治疗指数。
Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization.
作者信息
Varona José F, Landete Pedro, Lopez-Martin Jose A, Estrada Vicente, Paredes Roger, Guisado-Vasco Pablo, de Orueta Lucía Fernández, Torralba Miguel, Fortún Jesús, Vates Roberto, Barberán José, Clotet Bonaventura, Ancochea Julio, Carnevali Daniel, Cabello Noemí, Porras Lourdes, Gijón Paloma, Monereo Alfonso, Abad Daniel, Zúñiga Sonia, Sola Isabel, Rodon Jordi, Izquierdo-Useros Nuria, Fudio Salvador, Pontes María José, de Rivas Beatriz, Girón de Velasco Patricia, Sopesén Belén, Nieto Antonio, Gómez Javier, Avilés Pablo, Lubomirov Rubin, White Kris M, Rosales Romel, Yildiz Soner, Reuschl Ann-Kathrin, Thorne Lucy G, Jolly Clare, Towers Greg J, Zuliani-Alvarez Lorena, Bouhaddou Mehdi, Obernier Kirsten, Enjuanes Luis, Fernández-Sousa Jose M, Krogan Nevan J, Jimeno José M, García-Sastre Adolfo
出版信息
medRxiv. 2021 May 25:2021.05.25.21257505. doi: 10.1101/2021.05.25.21257505.
UNLABELLED
Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.5 mg/day for 3 days, as a 90-minute intravenous infusion) in 45 patients (15 per dose-cohort). Treatment was well tolerated, with only two Grade 3 treatment-related adverse events observed (hypersensitivity and diarrhea). The discharge rates by Days 8 and 15 were 56.8% and 81.8%, respectively, with data sustaining dose-effect. A mean 4.2 log10 viral load reduction was attained by Day 15. Improvement in inflammation markers was also noted in a seemingly dose-dependent manner. These results suggest that plitidepsin impacts the outcome of patients with COVID-19.
ONE-SENTENCE SUMMARY: Plitidepsin, an inhibitor of SARS-Cov-2 , is safe and positively influences the outcome of patients hospitalized with COVID-19.
未标注
普利替肽是一种源自海洋的环肽，通过靶向宿主蛋白eEF1A（真核翻译延伸因子1A），在低纳摩尔浓度下抑制SARS-CoV-2复制。我们评估了在住院的COVID-19成年患者中使用普利替肽的干预模型，对45名患者（每个剂量组15名）评估了三种剂量（1.5、2和2.5毫克/天，共3天，90分钟静脉输注）。治疗耐受性良好，仅观察到两例3级治疗相关不良事件（超敏反应和腹泻）。第8天和第15天的出院率分别为56.8%和81.8%，数据支持剂量效应。到第15天，病毒载量平均降低了4.2个log10。炎症标志物也以似乎剂量依赖的方式得到改善。这些结果表明普利替肽会影响COVID-19患者的预后。
一句话总结
SARS-CoV-2抑制剂普利替肽对COVID-19住院患者安全且对预后有积极影响。
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