美国西奈山伊坎医学院Adolfo García-Sastre等研究人员合作发现，plitidepsin通过靶向宿主蛋白eEF1A对SARS-CoV-2具有强大的临床前功效。2021年1月25日，《科学》杂志在线发表了这一最新研究成果。

研究人员发现，具有有限的临床批准的药物plitidepsin（aplidin）在体外对SARS-CoV-2的抗病毒活性（IC90=0.88 nM）比瑞德西韦27.5倍，并且在细胞培养中的毒性有限。通过使用抗药性突变体，研究人员表明，通过抑制已知的靶标eEF1，plitidepsin对SARS-CoV-2具有抗病毒活性。研究人员表明，在预防SARS-CoV-2感染的两种小鼠模型中，plitidepsin治疗具有体内功效，并可通过预防性治疗使肺中病毒复制减少了两个数量级。

这些结果表明，plitidepsin是COVID-19的潜在治疗候选药物。 

据了解，SARS-CoV-2病毒蛋白与真核翻译机器相互作用，并且翻译抑制剂具有有效的抗病毒作用。

附：英文原文

Title: Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A

Author: Kris M. White, Romel Rosales, Soner Yildiz, Thomas Kehrer, Lisa Miorin, Elena Moreno, Sonia Jangra, Melissa B. Uccellini, Raveen Rathnasinghe, Lynda Coughlan, Carles Martinez-Romero, Jyoti Batra, Ajda Rojc, Mehdi Bouhaddou, Jacqueline M. Fabius, Kirsten Obernier, Marion Dejosez, María José Guillén, Alejandro Losada, Pablo Avilés, Michael Schotsaert, Thomas Zwaka, Marco Vignuzzi, Kevan M. Shokat, Nevan J. Krogan, Adolfo García-Sastre

Issue&Volume: 2021/01/25

Abstract: SARS-CoV-2 viral proteins interact with the eukaryotic translation machinery and inhibitors of translation have potent antiviral effects. Here we report that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (IC90 = 0.88 nM) 27.5-fold more potent than remdesivir against SARS-CoV-2 in vitro, with limited toxicity in cell culture. Through the use of a drug resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A. We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.

DOI: 10.1126/science.abf4058

Source: https://science.sciencemag.org/content/early/2021/01/22/science.abf4058