Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro.

Autor: Radoshitzky SR; The Geneva Foundation, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA.; Division of Antivirals, Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA., Iversen P; The Geneva Foundation, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA., Lu X; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Zou J; Department of Biochemistry & Molecular Biology, Institute for Drug Discovery, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA., Kaptein SJF; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000, Leuven, Belgium.; Global Virus Network, GVN, Baltimore, USA., Stuthman KS; The Geneva Foundation, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA., Van Tongeren SA; The Geneva Foundation, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA., Steffens J; The Geneva Foundation, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA., Gong R; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Truong H; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Sapre AA; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Yang H; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Xie X; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Chia JJ; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Song ZJ; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Leventhal SM; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Chan J; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Shornikov A; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Zhang X; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000, Leuven, Belgium.; Global Virus Network, GVN, Baltimore, USA., Cowfer D; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Yu H; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Warren T; The Geneva Foundation, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA.; Laulima Government Solutions, LLC., Orlando, FL, USA., Cihlar T; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Porter DP; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Neyts J; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, B-3000, Leuven, Belgium.; Global Virus Network, GVN, Baltimore, USA., Shi PY; Department of Biochemistry & Molecular Biology, Institute for Drug Discovery, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA., Wells J; The Geneva Foundation, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, USA., Bilello JP; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA., Feng JY; Gilead Sciences, Inc, 333 Lakeside Drive, Foster City, CA, USA. joy.feng@gilead.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Feb 23; Vol. 13 (1), pp. 3131. Date of Electronic Publication: 2023 Feb 23.
DOI: 10.1038/s41598-023-29517-9
Abstrakt: Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). Remdesivir is taken up by target cells and metabolized in multiple steps to form the active nucleoside triphosphate (GS-443902), which acts as a potent inhibitor of viral RNA-dependent RNA polymerases. Remdesivir and GS-441524 have antiviral activity against multiple RNA viruses. Here, we expand the evaluation of remdesivir's antiviral activity to members of the families Flaviviridae, Picornaviridae, Filoviridae, Orthomyxoviridae, and Hepadnaviridae. Using cell-based assays, we show that remdesivir can inhibit infection of flaviviruses (such as dengue 1-4, West Nile, yellow fever, Zika viruses), picornaviruses (such as enterovirus and rhinovirus), and filoviruses (such as various Ebola, Marburg, and Sudan virus isolates, including novel geographic isolates), but is ineffective or is significantly less effective against orthomyxoviruses (influenza A and B viruses), or hepadnaviruses B, D, and E. In addition, remdesivir shows no antagonistic effect when combined with favipiravir, another broadly acting antiviral nucleoside analog, and has minimal interaction with a panel of concomitant medications. Our data further support remdesivir as a broad-spectrum antiviral agent that has the potential to address multiple unmet medical needs, including those related to antiviral pandemic preparedness.
(© 2023. The Author(s).)
Databáze: MEDLINE
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