Remdesivir inhibits the polymerases of the novel filoviruses Lloviu and Bombali virus
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 current...
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| Published in: | Antiviral research Vol. 192; p. 105120 |
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| Main Authors: | , , , , , |
| Format: | Journal Article |
| Language: | English |
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01-08-2021
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| 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 IC50 values to its activity against EBOV. This suggests that treatment with remdesivir might represent a viable option in case of infections with novel filoviruses.
•Remdesivir is a highly promising antiviral against Ebola virus, but its activity against novel filoviruses was unknown.•a minigenome system was generated for the novel filovirus Bombali virus, allowing assessment of viral polymerase activity.•Using this and existing minigenome systems remdesivir was shown to also be active against Bombali, Lloviu, and Reston virus.•This suggests remdesivir as a treatment against novel filoviruses for which antibody-based therapies are unavailable. |
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| AbstractList | 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 IC50 values to its activity against EBOV. This suggests that treatment with remdesivir might represent a viable option in case of infections with novel filoviruses.
•Remdesivir is a highly promising antiviral against Ebola virus, but its activity against novel filoviruses was unknown.•a minigenome system was generated for the novel filovirus Bombali virus, allowing assessment of viral polymerase activity.•Using this and existing minigenome systems remdesivir was shown to also be active against Bombali, Lloviu, and Reston virus.•This suggests remdesivir as a treatment against novel filoviruses for which antibody-based therapies are unavailable. |
| ArticleNumber | 105120 |
| Author | Bodmer, Bianca S. Wendt, Lisa Zierke, Lukas Groseth, Allison Hoenen, Thomas Greßler, Josephin |
| Author_xml | – sequence: 1 givenname: Bianca S. orcidid: 0000-0001-9695-9168 surname: Bodmer fullname: Bodmer, Bianca S. – sequence: 2 givenname: Lukas surname: Zierke fullname: Zierke, Lukas – sequence: 3 givenname: Lisa orcidid: 0000-0002-0390-5820 surname: Wendt fullname: Wendt, Lisa – sequence: 4 givenname: Josephin surname: Greßler fullname: Greßler, Josephin – sequence: 5 givenname: Allison orcidid: 0000-0001-9528-5130 surname: Groseth fullname: Groseth, Allison – sequence: 6 givenname: Thomas orcidid: 0000-0002-5829-6305 surname: Hoenen fullname: Hoenen, Thomas email: thomas.hoenen@fli.de |
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| Keywords | Ebola virus Antiviral therapy Remdesivir Bombali virus Lloviu virus Reston virus |
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