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author Jimeno, Jose
Varona, Jose Felipe
Lopez-Martin, Jose A
Izquierdo-Useros, Nuria
Molina Molina, Elisa
Guisado-Vasco, Pablo
Sachse, Martin
Risco, Cristina
Losada, Alejandro
Fudio, Salvador
Luepke, Erik
Nieto, Antonio
Gomez, Javier
Aviles, Pablo
Cuevas, Carmen
Bouhaddou, Mehdi
Sola, Isabel
Krogan, Nevan J
Enjuanes, Luis
Fernandez-Sousa, Jose M
GarcÍa-Sastre, Adolfo
White, Kris
author_facet Jimeno, Jose
Varona, Jose Felipe
Lopez-Martin, Jose A
Izquierdo-Useros, Nuria
Molina Molina, Elisa
Guisado-Vasco, Pablo
Sachse, Martin
Risco, Cristina
Losada, Alejandro
Fudio, Salvador
Luepke, Erik
Nieto, Antonio
Gomez, Javier
Aviles, Pablo
Cuevas, Carmen
Bouhaddou, Mehdi
Sola, Isabel
Krogan, Nevan J
Enjuanes, Luis
Fernandez-Sousa, Jose M
GarcÍa-Sastre, Adolfo
White, Kris
Jimeno, Jose
Varona, Jose Felipe
Lopez-Martin, Jose A
Izquierdo-Useros, Nuria
Molina Molina, Elisa
Guisado-Vasco, Pablo
Sachse, Martin
Risco, Cristina
Losada, Alejandro
Fudio, Salvador
Luepke, Erik
Nieto, Antonio
Gomez, Javier
Aviles, Pablo
Cuevas, Carmen
Bouhaddou, Mehdi
Sola, Isabel
Krogan, Nevan J
Enjuanes, Luis
Fernandez-Sousa, Jose M
GarcÍa-Sastre, Adolfo
White, Kris
collection PubMed - marine biology
contents Pharmacological reprogramming of plitidepsin as a SARS-CoV-2 inhibitor. Jimeno, Jose Varona, Jose Felipe Lopez-Martin, Jose A Izquierdo-Useros, Nuria Molina Molina, Elisa Guisado-Vasco, Pablo Sachse, Martin Risco, Cristina Losada, Alejandro Fudio, Salvador Luepke, Erik Nieto, Antonio Gomez, Javier Aviles, Pablo Cuevas, Carmen Bouhaddou, Mehdi Sola, Isabel Krogan, Nevan J Enjuanes, Luis Fernandez-Sousa, Jose M GarcÍa-Sastre, Adolfo White, Kris Humans Depsipeptides SARS-CoV-2 Antiviral Agents COVID-19 Peptides, Cyclic Animals COVID-19 Drug Treatment Pandemics Betacoronavirus Drug Repositioning Coronavirus Infections Clinical Trials as Topic Pneumonia, Viral Selective pressures in the ocean promote the evolution of potent molecules that may be useful in therapeutic settings. Tunicates provide a rich source of bioactive molecules that have been shown to have anti-neoplastic and anti-microbial activities. Plitidepsin, a natural marine cyclic depsipeptide originally isolated from the tunicate Aplidium albicans, was originally developed as an anti-tumor drug, and has been approved for use in Australia in patients with advanced pretreated myeloma. Early in the SARS-CoV-2 pandemic, plitidepsin was shown to have potent preclinical efficacy against the virus, suggesting that it could be repurposed for the treatment of COVID-19. This review summarizes the clinical development of plitidepsin first as an anti-tumor drug, before providing a recapitulation of current efforts to repurpose the molecule as an antiviral therapy. The pharmacokinetic and pharmacodynamic data on plitidepsin will be analyzed, and the various experimental lines of evidence in support of the molecule's multifactorial mechanism of action will be explored. Finally, the available data on the use of plitidepsin in patients with COVID-19 will be presented, including results from a Phase I proof-of-concept study, real-world data from immunocompromised patients, and a look of results from a Phase III clinical trial that confirms the working hypothesis.
format Artículo científico
id pubmed_41218566
institution PubMed
language en
publishDate 2025
publisher Molecular aspects of medicine
record_format pubmed
spellingShingle Pharmacological reprogramming of plitidepsin as a SARS-CoV-2 inhibitor.
Jimeno, Jose
Varona, Jose Felipe
Lopez-Martin, Jose A
Izquierdo-Useros, Nuria
Molina Molina, Elisa
Guisado-Vasco, Pablo
Sachse, Martin
Risco, Cristina
Losada, Alejandro
Fudio, Salvador
Luepke, Erik
Nieto, Antonio
Gomez, Javier
Aviles, Pablo
Cuevas, Carmen
Bouhaddou, Mehdi
Sola, Isabel
Krogan, Nevan J
Enjuanes, Luis
Fernandez-Sousa, Jose M
GarcÍa-Sastre, Adolfo
White, Kris
Humans
Depsipeptides
SARS-CoV-2
Antiviral Agents
COVID-19
Peptides, Cyclic
Animals
COVID-19 Drug Treatment
Pandemics
Betacoronavirus
Drug Repositioning
Coronavirus Infections
Clinical Trials as Topic
Pneumonia, Viral
Pharmacological reprogramming of plitidepsin as a SARS-CoV-2 inhibitor. Jimeno, Jose Varona, Jose Felipe Lopez-Martin, Jose A Izquierdo-Useros, Nuria Molina Molina, Elisa Guisado-Vasco, Pablo Sachse, Martin Risco, Cristina Losada, Alejandro Fudio, Salvador Luepke, Erik Nieto, Antonio Gomez, Javier Aviles, Pablo Cuevas, Carmen Bouhaddou, Mehdi Sola, Isabel Krogan, Nevan J Enjuanes, Luis Fernandez-Sousa, Jose M GarcÍa-Sastre, Adolfo White, Kris Humans Depsipeptides SARS-CoV-2 Antiviral Agents COVID-19 Peptides, Cyclic Animals COVID-19 Drug Treatment Pandemics Betacoronavirus Drug Repositioning Coronavirus Infections Clinical Trials as Topic Pneumonia, Viral Selective pressures in the ocean promote the evolution of potent molecules that may be useful in therapeutic settings. Tunicates provide a rich source of bioactive molecules that have been shown to have anti-neoplastic and anti-microbial activities. Plitidepsin, a natural marine cyclic depsipeptide originally isolated from the tunicate Aplidium albicans, was originally developed as an anti-tumor drug, and has been approved for use in Australia in patients with advanced pretreated myeloma. Early in the SARS-CoV-2 pandemic, plitidepsin was shown to have potent preclinical efficacy against the virus, suggesting that it could be repurposed for the treatment of COVID-19. This review summarizes the clinical development of plitidepsin first as an anti-tumor drug, before providing a recapitulation of current efforts to repurpose the molecule as an antiviral therapy. The pharmacokinetic and pharmacodynamic data on plitidepsin will be analyzed, and the various experimental lines of evidence in support of the molecule's multifactorial mechanism of action will be explored. Finally, the available data on the use of plitidepsin in patients with COVID-19 will be presented, including results from a Phase I proof-of-concept study, real-world data from immunocompromised patients, and a look of results from a Phase III clinical trial that confirms the working hypothesis.
title Pharmacological reprogramming of plitidepsin as a SARS-CoV-2 inhibitor.
topic Humans
Depsipeptides
SARS-CoV-2
Antiviral Agents
COVID-19
Peptides, Cyclic
Animals
COVID-19 Drug Treatment
Pandemics
Betacoronavirus
Drug Repositioning
Coronavirus Infections
Clinical Trials as Topic
Pneumonia, Viral
url https://pubmed.ncbi.nlm.nih.gov/41218566/