Promising drug candidates for Crimean-Congo haemorrhagic fever
identified

Date:
April 19, 2022
Source:
Karolinska Institutet
Summary:
Researchers have identified key signalling pathways that when
blocked by existing drug candidates limit reproduction of the
Crimean-Congo haemorrhagic fever (CCHF) virus. The findings offer
hope for patients affected by this potentially deadly disease.



FULL STORY ========================================================================== Researchers at Karolinska Institutet in Sweden have identified key
signalling pathways that when blocked by existing drug candidates limit reproduction of the Crimean-Congo haemorrhagic fever (CCHF) virus. The findings, published in the journal eLife, offer hope for patients affected
by this potentially deadly disease.


==========================================================================
"The spread of the CCHF virus poses an increased threat to public health
due to its high mortality rate in humans, which varies between 3 to as
much as 40 per cent in some regions," says the study's senior author Ali Mirazimi, adjunct professor at the Department of Laboratory Medicine, Karolinska Institutet.

"Unfortunately, there are currently no vaccines or effective treatments available, which is why it is of utmost urgency to identify promising
drug candidates that could lead to better treatments and reduce the high mortality rate." The CCHF virus is primarily transmitted to people
from tick bites or through contact with infected animals, although human-to-human transmission can also occur. The virus causes the disease Crimean-Congo haemorrhagic fever, which typically manifests itself with symptoms such as fever, muscle aches, joint pain, vomiting and bleeding,
and can progress to organ failure and death.

The disease is endemic with fairly stable infection levels in 30
countries in Central Asia, the Middle East, southeast Europe and parts
of Africa. However, with global warming, the ticks carrying the virus
are spreading to other parts of the world, with more cases seen in other
parts of Europe in recent years.

The disease is classified as hazardous to society according to the
Communicable Diseases Act.

Pathways identified All viruses are parasites that are completely
dependent on their hosts for reproduction. A virus that infects a cell reprograms the cell to create more virus. The cells' energy supply
and functions are controlled via signalling pathways, and viruses take advantage of these pathways to spread within the body.

In the study, the research group investigated how the CCHF virus infects
cells and what types of changes take place. Using blood samples from
patients with both acute infection and one year after recovery and cell
culture experiments, the researchers found that the CCHF virus prefers
pathways involving energy metabolism to reproduce.

Drug candidates reduce viral spread By blocking two key metabolic
pathways, glycolysis and glutaminolysis, with previously identified drug candidates, the researchers were able to significantly reduce viral reproduction in a laboratory setting. The findings build on earlier
research from the same research groups at Karolinska Institutet, including
a study that found similar mechanisms involved in the proliferation of SARS-CoV-2, which causes the disease COVID-19.

"We hope that our findings can lead to new antiviral treatments against Crimean-Congo haemorrhagic fever," says the study's first author Ujjwal
Neogi, researcher at the Department of Laboratory Medicine at Karolinska Institutet.

"Based on our discovery, we will soon begin in vivo studies in animals
and hopefully translate these findings into clinical trials in the near future." The study was supported by grants from the Swedish Research
Council, the Public Health England Grant In Aid, Karolinska Institutet
and the European Union Horizon 2020 CCHF Vaccine Grant.


========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Nazif Elaldi, Ujjwal Neogi, Sofia Appelberg, Anoop Ambikan,
Emma Kennedy,
Stuart Dowall, Binnur K Bagci, Soham Gupta, Jimmy E Rodriguez,
Sara Svensson-Akusja"rvi, Vanessa Monteil, Akos Vegvari, Rui
Benfeitas, Akhil Banerjea, Friedemann Weber, Roger Hewson,
Ali Mirazimi. Multi-omics insights into host-viral response and
pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel
therapeutic target. eLife, 2022; 11 DOI: 10.7554/eLife.76071 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220419103223.htm

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