Investigating the effect of ribavirin treatment on genetic mutations in Crimean–Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing

Jake D'Addiego; Nazif Elaldi; Nadina Wand; Karen Osman; Binnur Koksal Bagci; Emma Kennedy; Ayse Nur Pektas; Eilish Hart; Gillian Slack; Roger Hewson

doi:10.1002/jmv.28548

Investigating the effect of ribavirin treatment on genetic mutations in Crimean–Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing

Jake D'Addiego, Nazif Elaldi, Nadina Wand^*, Karen Osman, Binnur Koksal Bagci, Emma Kennedy, Ayse Nur Pektas, Eilish Hart, Gillian Slack, Roger Hewson

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Crimean–Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease. Samples collected from CCHF patients receiving ribavirin treatment or supportive care only at Sivas Cumhuriyet University Hospital, Turkey, were analysed. By comparing the frequency of mutations in each group, we found little evidence of an overall mutagenic effect. This suggests that ribavirin, administered at the acute stages of CCHFV infection (at the World Health Organization-recommended dose) is unable to induce lethal mutagenesis that would cause an extinction event in the CCHFV population and reduce viremia.

Original language	English
Article number	e28548
Journal	Journal of Medical Virology
Volume	95
Issue number	2
DOIs	https://doi.org/10.1002/jmv.28548
Publication status	Published - Feb 2023

Bibliographical note

Funding Information:
The study was funded by the Newton Fund: Institutional Links programme (grant number 527597374) through the British Council and TUBITAK (Turkey) ‐ Katip Çelebi between UK and Turkey (grant number 119N515), the Royal Society (grant number IES\R2\212130), and the H2020 CCHF Vaccine Project (grant number 723723). Part of this study was supported by Grant‐in‐Aid for New and Emerging Vector Borne and Zoonotic Disease from UK Health Security Agency (grant number 111752). The views expressed are those of the authors and not necessarily those of the funding bodies.

Publisher Copyright:
© 2023 Crown copyright and The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland.

Keywords

Crimean–Congo haemorrhagic fever virus
mutation
ribavirin
variant
whole genome next-generation sequencing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/jmv.28548

Cite this

D'Addiego, J., Elaldi, N., Wand, N., Osman, K., Bagci, B. K., Kennedy, E., Pektas, A. N., Hart, E., Slack, G., & Hewson, R. (2023). Investigating the effect of ribavirin treatment on genetic mutations in Crimean–Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing. Journal of Medical Virology, 95(2), Article e28548. https://doi.org/10.1002/jmv.28548

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abstract = "Crimean–Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease. Samples collected from CCHF patients receiving ribavirin treatment or supportive care only at Sivas Cumhuriyet University Hospital, Turkey, were analysed. By comparing the frequency of mutations in each group, we found little evidence of an overall mutagenic effect. This suggests that ribavirin, administered at the acute stages of CCHFV infection (at the World Health Organization-recommended dose) is unable to induce lethal mutagenesis that would cause an extinction event in the CCHFV population and reduce viremia.",

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note = "Funding Information: The study was funded by the Newton Fund: Institutional Links programme (grant number 527597374) through the British Council and TUBITAK (Turkey) ‐ Katip {\c C}elebi between UK and Turkey (grant number 119N515), the Royal Society (grant number IES\textbackslash{}R2\textbackslash{}212130), and the H2020 CCHF Vaccine Project (grant number 723723). Part of this study was supported by Grant‐in‐Aid for New and Emerging Vector Borne and Zoonotic Disease from UK Health Security Agency (grant number 111752). The views expressed are those of the authors and not necessarily those of the funding bodies. Publisher Copyright: {\textcopyright} 2023 Crown copyright and The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland.",

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AU - Slack, Gillian

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Investigating the effect of ribavirin treatment on genetic mutations in Crimean–Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing

Abstract

Bibliographical note

Keywords

UN SDGs

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