دورية أكاديمية
Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19
| العنوان: | Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19 |
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| المؤلفون: | Varona, Jose F., Landete, Pedro, Lopez-Martin, Jose A., Estrada, Vicente, Paredes, Roger, Guisado-Vasco, Pablo, Fernandez de Orueta, Lucia, Torralba, Miguel, Fortun, Jesus, Vates, Roberto, Barberan, Jose, Clotet, Bonaventura, Ancochea, Julio, Carnevali, Daniel, Cabello, Noemi, Porras, Lourdes, Gijon, Paloma, Monereo, Alfonso, Abad, Daniel, Zuñiga, Sonia, Sola, Isabel, Rodon, Jordi, Vergara-Alert, Julia, Izquierdo-Useros, Nuria, Fudio, Salvador, Pontes, Maria Jose, de Rivas, Beatriz, Giron de Velasco, Patricia, Nieto, Antonio, Gomez, Javier, Aviles, Pablo, Lubomirov, Rubin, Belgrano, Alvaro, Sopesen, Belen, White, Kris M., Rosales, Romel, Yildiz, Soner, Reuschl, Ann-Kathrin, Thorne, Lucy G., Jolly, Clare, Towers, Greg J., Zuliani-Alvarez, Lorena, Bouhaddou, Mehdi, Obernier, Kirsten, McGovern, Briana L., Rodriguez, M. Luis, Enjuanes, Luis, Fernandez-Sousa, Jose M., Krogan, Nevan J., Jimeno, Jose M., Garcia-Sastre, Adolfo |
| المساهمون: | Producció Animal, Sanitat Animal |
| بيانات النشر: | Life Science Alliance |
| سنة النشر: | 2022 |
| المجموعة: | IRTA Pubpro (Institute of Agrifood Research and Technology / Institut de Recerca i Tecnologia Agroalimentàries) |
| الوقت: | 619 |
| الوصف: | Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19. ; info:eu-repo/semantics/publishedVersion |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2575-1077 |
| العلاقة: | Life Science Alliance; Varona, Jose F, Pedro Landete, Jose A Lopez-Martin, Vicente Estrada, Roger Paredes, Pablo Guisado-Vasco, and Lucia Fernandez de Orueta et al. 2022. "Preclinical And Randomized Phase I Studies Of Plitidepsin In Adults Hospitalized With COVID-19". Life Science Alliance 5 (4): e202101200. doi:10.26508/lsa.202101200.; http://hdl.handle.net/20.500.12327/1670Test; https://doi.org/10.26508/lsa.202101200Test |
| DOI: | 10.26508/lsa.202101200 |
| الإتاحة: | https://doi.org/20.500.12327/1670Test https://doi.org/10.26508/lsa.202101200Test https://hdl.handle.net/20.500.12327/1670Test |
| حقوق: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.FB1E72C3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 25751077 |
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| DOI: | 10.26508/lsa.202101200 |