Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization

Varona, José F.; Landete, Pedro; López-Martín, José A.; Estrada, Vicente; Paredes, Roger; Guisado-Vasco, Pablo; Orueta, Lucía Fernández de; Torralba, Miguel; Fortün, Jesús; Vates, Roberto; Barberán, José; Clotet, Bonaventura; Ancochea, Julio; Carnevali, Daniel; Cabello, Noemí; Porras, Luis Fernando Barón; Gijón, Paloma; Monereo, A; Abad, Daniel; Zúñiga, Sonia; Sola, Isabel; Rodón, Jordi; Izquierdo-Useros, Núria; Fudio, Salvador; Pontes, María José; Rivas, Beatriz de; Velasco, Patricia Giron de; Sopesen, Belen; Nieto, Antonio Martínez; Gómez, Javier; Avilés, Pablo; Lubomirov, Rubin; White, Kris M.; Rosales, Romel; Yildiz, Soner; Reuschl, Ann-Kathrin; Thorne, Lucy; Jolly, Clare; Towers, Greg J.; Zuliani-Alvarez, Lorena; Bouhaddou, Mehdi; Obernier, Kirsten; Enjuanes, Luis; Fernández-Sousa, J.M.; Krogan, Nevan J.; Jimeno, J.; Garcı́a-Sastre, Adolfo

doi:10.1101/2021.05.25.21257505

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…The drug was shown to inhibit viral replication, including in mice infected with SARS-CoV-2. It should be noted that the antiviral activity of the drug against SARS-CoV-2 is 27.5 times more potent than that of Remdesivir [103,104], and relevant clinical findings suggest potential effectiveness [105]. The drug is currently undergoing clinical evaluation (phase 3) in combination with Dexamethasone in approximately 610 patients (ClinicalTrials.gov, NCT04784559).…”

Section: Plitidepsinmentioning

confidence: 99%

Clinically Evaluated COVID-19 Drugs with Therapeutic Potential for Biological Warfare Agents

Dechtman,

Ankory,

Sokolinsky

et al. 2023

Microorganisms

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak resulted in hundreds of millions of coronavirus cases, as well as millions of deaths worldwide. Coronavirus Disease 2019 (COVID-19), the disease resulting from exposure to this pathogen, is characterized, among other features, by a pulmonary pathology, which can progress to “cytokine storm”, acute respiratory distress syndrome (ARDS), respiratory failure and death. Vaccines are the unsurpassed strategy for prevention and protection against the SARS-CoV-2 infection. However, there is still an extremely high number of severely ill people from at-risk populations. This may be attributed to waning immune response, variant-induced breakthrough infections, unvaccinated population, etc. It is therefore of high importance to utilize pharmacological-based treatments, despite the progression of the global vaccination campaign. Until the approval of Paxlovid, an efficient and highly selective anti-SARS-CoV-2 drug, and the broad-spectrum antiviral agent Lagevrio, many pharmacological-based countermeasures were, and still are, being evaluated in clinical trials. Some of these are host-directed therapies (HDTs), which modulate the endogenic response against the virus, and therefore may confer efficient protection against a wide array of pathogens. These could potentially include Biological Warfare Agents (BWAs), exposure to which may lead to mass casualties due to disease severity and a possible lack of efficient treatment. In this review, we assessed the recent literature on drugs under advanced clinical evaluation for COVID-19 with broad spectrum activity, including antiviral agents and HDTs, which may be relevant for future coping with BWAs, as well as with other agents, in particular respiratory infections.

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Section: Plitidepsinmentioning

confidence: 99%

Clinically Evaluated COVID-19 Drugs with Therapeutic Potential for Biological Warfare Agents

Dechtman,

Ankory,

Sokolinsky

et al. 2023

Microorganisms

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“…Plitidepsin has shown very potent antiviral activity in vitro and is currently under Phase 3 clinical assays. Preliminary results have shown that it is safe and positively influences the outcome of patients hospitalized with COVID-19 [53].…”

Section: Plitidepsinmentioning

confidence: 99%

Approaches to the Potential Therapy of COVID-19: A General Overview from the Medicinal Chemistry Perspective

Menéndez

2022

Molecules

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In spite of advances in vaccination, control of the COVID-19 pandemic will require the use of pharmacological treatments against SARS-CoV2. Their development needs to consider the existence of two phases in the disease, namely the viral infection and the inflammatory stages. The main targets for antiviral therapeutic intervention are: (a) viral proteins, including the spike (S) protein characteristic of the viral cover and the viral proteases in charge of processing the polyprotein arising from viral genome translation; (b) host proteins, such as those involved in the processes related to viral entry into the host cell and the release of the viral genome inside the cell, the elongation factor eEF1A and importins. The use of antivirals targeted at host proteins is less developed but it has the potential advantage of not being affected by mutations in the genome of the virus and therefore being active against all its variants. Regarding drugs that address the hyperinflammatory phase of the disease triggered by the so-called cytokine storm, the following strategies are particularly relevant: (a) drugs targeting JAK kinases; (b) sphingosine kinase 2 inhibitors; (c) antibodies against interleukin 6 or its receptor; (d) use of the traditional anti-inflammatory corticosteroids.

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“…This functional activity against SARS-CoV-2 has been demonstrated in mouse models with a potent antiviral activity with limited toxicity (90% inhibitory concentration = 0.88 nM) ( White et al, 2021 ). Given the promising results obtained at the preclinical level, Dr. Fernandez Sousa-Faro and his team at Pharma Mar started a phase I/II dose-escalating clinical trial, which proved the efficiency of the treatment, especially in patients with moderate infection ( Varona et al, 2021 , 2022 ). Given these results, PharmaMar recently obtained authorization to start a phase III clinical trial (NEPTUNO) to determine the efficacy of plitidepsin for the treatment of hospitalized patients with moderate COVID-19 infection.…”

Section: Covid-19 Vaccines (1)mentioning

confidence: 99%

Alicante-Winter Immunology Symposium in Health (A-Wish) and the Boulle-SEI awards: A collaboration between the Spanish Society for immunology, the University of Alicante and the Jean Boulle Group to honor the Balmis Expedition

Ochando

Cámara

Durham³

et al. 2022

Current Research in Immunology

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Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization

Cited by 6 publications

References 39 publications

Clinically Evaluated COVID-19 Drugs with Therapeutic Potential for Biological Warfare Agents

Clinically Evaluated COVID-19 Drugs with Therapeutic Potential for Biological Warfare Agents

Approaches to the Potential Therapy of COVID-19: A General Overview from the Medicinal Chemistry Perspective

Alicante-Winter Immunology Symposium in Health (A-Wish) and the Boulle-SEI awards: A collaboration between the Spanish Society for immunology, the University of Alicante and the Jean Boulle Group to honor the Balmis Expedition

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