Researchers in Sweden have identified a signaling pathway that, when blocked by existing drug candidates, limited reproduction of the Crimean-Congo haemorrhagic fever (CCHF) virus. The findings offer hope for patients affected by the potentially deadly disease.
CCHF is primarily transmitted to people from tick bites or through contact with infected animals, although human-to-human transmission can also occur. It typically presents 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. The disease is classified as hazardous to society according to the Communicable Diseases Act.
“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 percent in some regions,” says Ali Mirazimi, coauthor of the study and adjunct professor at the Karolinska Institutet’s Department of Laboratory Medicine. “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.”
Using blood samples from patients with both acute CCHF infection and one year after recovery along with cell culture experiments, the researchers found that the virus prefers pathways involving energy metabolism to reproduce.
By blocking metabolic pathways glycolysis and glutaminolysis with existing drug candidates, the researchers were able to significantly reduce viral reproduction in a laboratory setting. The findings build on earlier research from Karolinska Institutet, including a study that found similar mechanisms involved in the proliferation of SARS-CoV-2, which causes the COVID-19.
“We hope that our findings can lead to new antiviral treatments against Crimean-Congo haemorrhagic fever,” says Ujjwal Neogi, also a researcher at Karolinska Institutet’s Department of Laboratory Medicine. “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 published recently in eLife.