New research has identified key signalling pathways that, when blocked by existing drug candidates, limit the reproduction of the Crimean-Congo haemorrhagic fever virus.
Crimean-Congo haemorrhagic fever is caused by a tick-borne virus in the family Bunyaviridae. The onset is sudden with symptoms such as headache, high fever, back pain, joint pain, stomach pain and vomiting. However, it 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 findings were published in the journal eLife and provide new hope for patients experiencing Crimean-Congo haemorrhagic fever.
Identifying virus pathways
With all viruses being parasites that are completely dependent on their hosts for reproduction, a virus infects a cell and then reprogrammes it to multiply. 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 researchers investigated how the Crimean-Congo haemorrhagic fever virus infects cells and what types of changes occur. The team used blood samples from patients with both acute infection and one year following recovery and cell culture experiments. The researchers discover that Crimean-Congo haemorrhagic fever virus favours pathways involving energy metabolism to reproduce.
“The spread of the CCHF virus poses an increased threat to public health due to its high mortality rate in humans, which varies between three to as much as 40% in some regions,” said 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.”
Potential drugs for Crimean-Congo haemorrhagic fever
The researchers found that 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 positive developments build on previous research from the researchers 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,” said the study’s first author Ujjwal Neogi, a 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.”
