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Plitidepsin: Mechanisms and Clinical Profile of a Promising Antiviral Agent against COVID-19.
Papapanou, Michail; Papoutsi, Eleni; Giannakas, Timoleon; Katsaounou, Paraskevi.
  • Papapanou M; School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
  • Papoutsi E; Society of Junior Doctors, 15123 Athens, Greece.
  • Giannakas T; School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
  • Katsaounou P; School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
J Pers Med ; 11(7)2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1314680
ABSTRACT
Current standard treatment of COVID-19 lacks in effective antiviral options. Plitidepsin, a cyclic depsipeptide authorized in Australia for patients with refractory multiple myeloma, has recently emerged as a candidate anti-SARS-CoV-2 agent. The aim of this review was to summarize current knowledge on plitidepsin's clinical profile, anti-tumour and anti-SARS-CoV-2 mechanisms and correlate this with available or anticipated, preclinical or clinical evidence on the drug's potential for COVID-19 treatment.PubMed, Scopus, CENTRAL, clinicaltrials.gov, medRxiv and bioRxiv databases were searched.Plitidepsinexerts its anti-tumour and antiviral properties primarily through acting on isoforms of the host cell's eukaryotic-translation-elongation-factor-1-alpha (eEF1A). Through inhibiting eEF1A and therefore translation of necessary viral proteins, it behaves as a "host-directed" anti-SARS-CoV-2 agent. In respect to its potent anti-SARS-CoV-2 properties, the drug has demonstrated superior ex vivo efficacy compared to other host-directed agents and remdesivir, and it might retain its antiviral effect against the more transmittable B.1.1.7 variant. Its well-studied safety profile, also in combination with dexamethasone, may accelerate its repurposing chances for COVID-19 treatment. Preliminary findings in hospitalized COVID-19 patients, have suggested potential safety and efficacy of plitidepsin, in terms of viral load reduction and clinical resolution. However, the still incomplete understanding of its exact integration into host cell-SARS-CoV-2 interactions, its intravenous administration exclusively purposing it for hospital settings the and precocity of clinical data are currently considered its chief deficits. A phase III trial is being planned to compare the plitidepsin-dexamethasone regimen to the current standard of care only in moderately affected hospitalized patients. Despite plitidepsin's preclinical efficacy, current clinical evidence is inadequate for its registration in COVID-19 patients.Therefore, multicentre trials on the drug's efficacy, potentially also studying populations of emerging SARS-CoV-2 lineages, are warranted.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Randomized controlled trials Topics: Variants Language: English Year: 2021 Document Type: Article Affiliation country: Jpm11070668

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Prognostic study / Randomized controlled trials Topics: Variants Language: English Year: 2021 Document Type: Article Affiliation country: Jpm11070668