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

• DOI: 10.1126/science.abf4058
• Publication Date: 2021-02-25T20:10:28Z
• Authors: Kris M. White; Romel Rosales; Soner Yildiz; Thomas Kehrer; Lisa Miorin; Elena Moreno; Sonia Jangra; Melissa B. Uccellini; Raveen Rathnasinghe; Lynda Coughlan; Carles Martinez-R...; 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
• Keywords: 2019-20 coronavirus outbreak

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of have potent antiviral effects. We found that drug plitidepsin (aplidin), which has limited clinical approval, possesses activity (90% inhibitory concentration = 0.88 nM) is more than remdesivir against SARS-CoV-2 in vitro by a factor 27.5, toxicity cell culture. Through use drug-resistant mutant, we show mediated through inhibition known target eEF1A (eukaryotic elongation 1A). demonstrate vivo efficacy treatment two mouse models infection reduction replication lungs orders magnitude using prophylactic treatment. Our results indicate promising therapeutic candidate for COVID-19.