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 demon-strated
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