Plitidepsin: a Repurposed Drug for the Treatment of COVID-19

Abstract

Finding antivirals to reduce coronavirus disease 2019 (COVID-19) morbidity and mortality has been challenging. Large randomized clinical trials that aimed to test four repurposed drugs, hydroxychloroquine, lopinavir-ritonavir, interferon beta 1a, and remdesivir, have shown that these compounds lack an impact on the COVID-19 course. Although the phase III COVID-19 vaccine trial results are encouraging, the search for effective COVID-19 therapeutics should not stop. Recently, plitidepsin (aplidin) demonstrated highly effective preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its antiviral activity was 27.5-fold more potent than that of remdesivir (K. M. White, R. Rosales, S. Yildiz, T. Kehrer, et al., Science, 2021, https://science.sciencemag.org/content/early/2021/01/22/science.abf4058). Plitidepsin, a repurposed drug developed for the treatment of multiple myeloma, targets the host translation cofactor eEF1A. Plitidepsin has shown efficacy in animal models and phase I/II human trials. Although plitidepsin is administered intravenously and its toxicity profile remains to be fully characterized, this compound may be a promising alternative COVID-19 therapeutic.