Oral administration of obeldesivir protects nonhuman primates against Sudan ebolavirus .

Autor: Cross RW; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Woolsey C; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Chu VC; Gilead Sciences, Inc., Foster City, CA, USA., Babusis D; Gilead Sciences, Inc., Foster City, CA, USA., Bannister R; Gilead Sciences, Inc., Foster City, CA, USA., Vermillion MS; Gilead Sciences, Inc., Foster City, CA, USA., Geleziunas R; Gilead Sciences, Inc., Foster City, CA, USA., Barrett KT; Gilead Sciences, Inc., Foster City, CA, USA., Bunyan E; Gilead Sciences, Inc., Foster City, CA, USA., Nguyen AQ; Gilead Sciences, Inc., Foster City, CA, USA., Cihlar T; Gilead Sciences, Inc., Foster City, CA, USA., Porter DP; Gilead Sciences, Inc., Foster City, CA, USA., Prasad AN; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Deer DJ; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Borisevich V; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Agans KN; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Martinez J; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Harrison MB; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Dobias NS; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Fenton KA; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA., Bilello JP; Gilead Sciences, Inc., Foster City, CA, USA., Geisbert TW; Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Mar 15; Vol. 383 (6688), pp. eadk6176. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1126/science.adk6176
Abstrakt: Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS-441524, have similar in vitro antiviral activity against filoviruses, including Marburg virus, Ebola virus, and Sudan virus (SUDV). We also report that once-daily oral ODV treatment of cynomolgus monkeys for 10 days beginning 24 hours after SUDV exposure confers 100% protection against lethal infection. Transcriptomics data show that ODV treatment delayed the onset of inflammation and correlated with antigen presentation and lymphocyte activation. Our results offer promise for the further development of ODV to control outbreaks of filovirus disease more rapidly.
Databáze: MEDLINE
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