biostudies-literatureVarona JFDefense Advanced Research Projects AgencyJPB Foundation, Open Philanthropy ProjectNIAID NIH HHSNational Institutes of HealthNIAIDPharmaMarRoddenberry Foundation, QCRG philanthropic donorsExcellence in Research AwardMedical Research CouncilDoDGovernment of SpainDARPAWellcome TrustCRIPT, NIAID supported Center of Excellence for Influenza Research and Responsee202101200https://www.ebi.ac.uk/biostudies/studies/S-EPMC8761492biostudies-literatureUnknown5(4)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 selectionLife science alliancePreclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.PMC8761492MR/W005611/1220863/Z/20/ZP50 AI150476HR0011-19-2-0020#HR0011-19-2-0020#133122PU19 AI135990U19 AI135972214344/Z/18/ZP01 AI06330275N93021C00014W81XWH-20-1-0270P50AI150476, U19AI135990, U19AI135972, R01AI143292, R01AI120694, and P01AI063302PIE_INTRAMURAL_ LINEA 1 - 202020E079; PIE_INTRAMURAL_CSIC-202020E0432020-215611 (5384)108079/Z/15/ZR01 AI143292R01 AI120694U19 AI142733MR/S023380/1U19AI142733, U19AI135972Reuschl AKParedes RTorralba MLopez-Martin JAAviles PJolly CMonereo ACarnevali DWhite KMVates RKrogan NJAncochea JSola IRodon JGiron de Velasco PClotet BAbad DEnjuanes LBarberan JLubomirov RZuliani-Alvarez LSopesen BGarcia-Sastre AVergara-Alert JBelgrano ABouhaddou MPorras LObernier Kde Rivas BNieto AMcGovern BLLandete PPontes MJFudio SRosales RGijon PCabello NFernandez-Sousa JMIzquierdo-Useros NTowers GJFortun JThorne LGZuniga SJimeno JMGomez JEstrada VFernandez de Orueta LGuisado-Vasco PYildiz SVarona JFRodriguez MLfalsePreclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.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 selection2022-01-01T00:00:00Z2022 Apr2026-05-09T07:21:14.924Z2022-02-11T16:06:58.537ZS-EPMC87614923501296210.26508/lsa.202101200