1. Remdesivir inhibits the polymerases of the novel filoviruses Lloviu and Bombali virus.
- Author
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Bodmer BS, Zierke L, Wendt L, Greßler J, Groseth A, and Hoenen T
- Subjects
- Adenosine Monophosphate pharmacology, Alanine pharmacology, Cell Line, Ebolavirus drug effects, Filoviridae classification, Filoviridae genetics, Humans, Inhibitory Concentration 50, Phylogeny, Virus Replication drug effects, Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Antiviral Agents pharmacology, Filoviridae drug effects, RNA-Dependent RNA Polymerase antagonists & inhibitors
- Abstract
In recent years, a number of novel filoviruses (e.g. Lloviu virus (LLOV) and Bombali virus (BOMV)) have been discovered. While antibody-based therapeutics have recently been approved for treatment of infections with the filovirus Ebola virus (EBOV), no treatment options for novel filoviruses currently exist. Further, the development of antivirals against them is complicated by the fact that only sequence information, but no actual virus isolates, are available. To address this issue, we developed a reverse genetics-based minigenome system for BOMV, which allows us to assess the activity of the BOMV polymerase. Together with similar systems that we have developed for other filoviruses in the past (i.e. LLOV and Reston virus (RESTV)), we then assessed the efficiency of remdesivir, a known inhibitor of the EBOV polymerase that has recently been tested in a clinical trial for efficacy against Ebola disease. We show that remdesivir is indeed also active against the polymerases of BOMV, LLOV, and RESTV, with comparable IC
50 values to its activity against EBOV. This suggests that treatment with remdesivir might represent a viable option in case of infections with novel filoviruses., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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