Abstract

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.

Details

Title
Expanded profiling of Remdesivir as a broad-spectrum antiviral and low potential for interaction with other medications in vitro
Author
Radoshitzky, Sheli R. 1 ; Iversen, Patrick 2 ; Lu, Xianghan 3 ; Zou, Jing 4 ; Kaptein, Suzanne J. F. 5 ; Stuthman, Kelly S. 2 ; Van Tongeren, Sean A. 2 ; Steffens, Jesse 2 ; Gong, Ruoyu 3 ; Truong, Hoa 3 ; Sapre, Annapurna A. 3 ; Yang, Huiling 3 ; Xie, Xiaodong 3 ; Chia, Jia Jun 3 ; Song, Zhijuan J. 3 ; Leventhal, Stacey M. 3 ; Chan, Josolyn 3 ; Shornikov, Alex 3 ; Zhang, Xin 5 ; Cowfer, David 3 ; Yu, Helen 3 ; Warren, Travis 6 ; Cihlar, Tomas 3 ; Porter, Danielle P. 3 ; Neyts, Johan 5 ; Shi, Pei-Yong 4 ; Wells, Jay 2 ; Bilello, John P. 3 ; Feng, Joy Y. 3 

 United States Army Medical Research Institute of Infectious Diseases (USAMRIID), The Geneva Foundation, Frederick, USA (GRID:grid.416900.a) (ISNI:0000 0001 0666 4455); Division of Antivirals, Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, USA (GRID:grid.483500.a) (ISNI:0000 0001 2154 2448) 
 United States Army Medical Research Institute of Infectious Diseases (USAMRIID), The Geneva Foundation, Frederick, USA (GRID:grid.416900.a) (ISNI:0000 0001 0666 4455) 
 Gilead Sciences, Inc, Foster City, USA (GRID:grid.418227.a) (ISNI:0000 0004 0402 1634) 
 University of Texas Medical Branch, Department of Biochemistry & Molecular Biology, Institute for Drug Discovery, Sealy Center for Structural Biology & Molecular Biophysics, Galveston, USA (GRID:grid.176731.5) (ISNI:0000 0001 1547 9964) 
 Rega Institute for Medical Research, KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Leuven, Belgium (GRID:grid.415751.3); GVN, Global Virus Network, Baltimore, USA (GRID:grid.475149.a) 
 United States Army Medical Research Institute of Infectious Diseases (USAMRIID), The Geneva Foundation, Frederick, USA (GRID:grid.416900.a) (ISNI:0000 0001 0666 4455); Laulima Government Solutions, LLC., Orlando, USA (GRID:grid.416900.a) 
Pages
3131
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2779291240
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.