6 research outputs found
Plitidepsin: Mechanisms and Clinical Profile of a Promising Antiviral Agent against COVID-19
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
Plitidepsin: Mechanisms and Clinical Profile of a Promising Antiviral Agent against COVID-19
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
Effect of COVID-19-Related Lockdown οn Hospital Admissions for Asthma and COPD Exacerbations: Associations with Air Pollution and Patient Characteristics
We conducted a retrospective observational study to assess the hospitalization rates for acute exacerbations of asthma and COPD (chronic obstructive pulmonary disease) during the first imposed lockdown in Athens, Greece. Patient characteristics and the concentration of eight air pollutants [namely, NO (nitrogen monoxide), NO2 (nitrogen dioxide), CO (carbon monoxide), PM2.5 (particulate matter 2.5), PM10 (particulate matter 10), O3 (ozone), SO2 (sulfur dioxide) and benzene] were considered. A total of 153 consecutive hospital admissions were studied. Reduced admissions occurred in the Lockdown period compared to the Pre-lockdown 2020 (p < 0.001) or the Control 2019 (p = 0.007) period. Furthermore, the concentration of 6/8 air pollutants positively correlated with weekly hospital admissions in 2020 and significantly decreased during the lockdown. Finally, admitted patients for asthma exacerbation during the lockdown were younger (p = 0.046) and less frequently presented respiratory failure (p = 0.038), whereas patients with COPD presented higher blood eosinophil percentage (p = 0.017) and count (p = 0.012). Overall, admissions for asthma and COPD exacerbations decreased during the lockdown. This might be partially explained by reduction of air pollution during this period while medical care avoidance behavior, especially among elderly patients cannot be excluded. Our findings aid in understanding the untold impact of the pandemic on diseases beyond COVID-19, focusing on patients with obstructive diseases
Effect of COVID-19-Related Lockdown on Hospital Admissions for Asthma and COPD Exacerbations: Associations with Air Pollution and Patient Characteristics
We conducted a retrospective observational study to assess the
hospitalization rates for acute exacerbations of asthma and COPD
(chronic obstructive pulmonary disease) during the first imposed
lockdown in Athens, Greece. Patient characteristics and the
concentration of eight air pollutants [namely, NO (nitrogen monoxide),
NO2 (nitrogen dioxide), CO (carbon monoxide), PM2.5 (particulate matter
2.5), PM10 (particulate matter 10), O-3 (ozone), SO2 (sulfur dioxide)
and benzene] were considered. A total of 153 consecutive hospital
admissions were studied. Reduced admissions occurred in the Lockdown
period compared to the Pre-lockdown 2020 (p < 0.001) or the Control 2019
(p = 0.007) period. Furthermore, the concentration of 6/8 air pollutants
positively correlated with weekly hospital admissions in 2020 and
significantly decreased during the lockdown. Finally, admitted patients
for asthma exacerbation during the lockdown were younger (p = 0.046) and
less frequently presented respiratory failure (p = 0.038), whereas
patients with COPD presented higher blood eosinophil percentage (p =
0.017) and count (p = 0.012). Overall, admissions for asthma and COPD
exacerbations decreased during the lockdown. This might be partially
explained by reduction of air pollution during this period while medical
care avoidance behavior, especially among elderly patients cannot be
excluded. Our findings aid in understanding the untold impact of the
pandemic on diseases beyond COVID-19, focusing on patients with
obstructive diseases