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

doi:10.1126/science.abf4058

GSTDTAP > 气候变化

DOI	10.1126/science.abf4058
	Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A
	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
	2021-02-26
发表期刊	Science
出版年	2021
英文摘要	Many host proteins play a role in the life cycle of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some are required for viral replication and translation. There are efforts toward finding drugs that target viral proteins, but a complementary approach is to target these required host proteins. White et al. explored the antiviral activity of the cyclic depsipeptide drug plitidepsin, which targets the hosts cell's translational machinery (see the Perspective by Wong and Damania). The authors show that in cells, the drug is substantially more potent than remdesivir against SARS-CoV-2, with limited cellular toxicity. Prophylactic treatment protected mice against SARS-CoV-2 infection, so further investigation of plitidepsin as a therapeutic is warranted. Science , this issue p. [926][1]; see also p. [884][2] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of translation have potent antiviral effects. We found that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (90% inhibitory concentration = 0.88 nM) that is more potent than remdesivir against SARS-CoV-2 in vitro by a factor of 27.5, 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 (eukaryotic translation elongation factor 1A). 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. [1]: /lookup/doi/10.1126/science.abf4058 [2]: /lookup/doi/10.1126/science.abg6837
领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：203[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/315939
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Kris M. White,Romel Rosales,Soner Yildiz,et al. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A[J]. Science,2021.
APA	Kris M. White.,Romel Rosales.,Soner Yildiz.,Thomas Kehrer.,Lisa Miorin.,...&Adolfo García-Sastre.(2021).Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A.Science.
MLA	Kris M. White,et al."Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A".Science (2021).