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Plitidepsin is a depsipeptide that was originally isolated from Aplidium albicans and has diverse biological activities.1,2,3 It binds to the α subunit isoform eEF1A2 of eukaryotic elongation factor 1 (eEF1; Kd = 79 nM) and inhibits the proliferation of NCI H460 non-small cell lung cancer (NSCLC) and HGC-27 gastric cancer cells (IC50s = 0.2 and 0.9 nM, respectively).1 Plitidepsin (0.01 nM) inhibits bone resorption by osteoclasts in a pit formation assay using bovine bone slices.2 It reduces viral titers and lung inflammation in the K18-hACE2 mouse model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection when administered at a dose of 0.3 mg/kg.3

1.Losada, A., Mu?oz-Alonso, M.J., García, G., et al.Translation elongation factor eEF1A2 is a novel anticancer target for the marine natural product plitidepsinSci. Rep.635100(2016) 2.Delgado-Calle, J., Kurihara, N., Atkinson, E.G., et al.Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclastsOncotarget10(28)2709-2721(2019) 3.White, K.M., Rosales, R., Yildiz, S., et al.Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1AScience371(6532)926-931(2021)

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