There is an urgent need to develop vaccines and antiviral drugs against Ebola virus and its cousin the Marburg virus – two of the deadliest and most contagious viruses in the world. Now, researchers have discovered that the way the Ebola and Marburg viruses try to enter host cells to replicate themselves can be blocked using a class of drugs that is already in common use.
The team – from the University of Illinois at Chicago (UIC) – publish their findings in the Journal of Virology.
Ebola and Marburg are the only two known members of a filovirus family called Filoviridae, which can cause severe hemorrhagic fever in humans and nonhuman primates.
According to the World Health Organization (WHO), the current outbreak of Ebola in West Africa is the largest and most complex since the virus was first discovered in 1976. Since the outbreak was first reported in March 2014, there have been 27,898 confirmed cases and 11,296 deaths.
Marburg was first identified in Marburg and Frankfurt in Germany and Belgrade in the former Yugoslavia. The victims were lab workers handling African green monkeys imported from Uganda. Fatality rates have varied greatly, from 25% to more than 80%.
The most recent outbreak of Marburg was in Uganda in 2014, where one man was confirmed to have the disease and died. The Ugandan government declared the country to be free of the virus in November 2014.
While the search for a vaccine is yielding results – for instance, Medical News Today recently learned of the first ever successful field test of an Ebola vaccine – there is still an urgent need for antiviral therapies to treat people who become infected and to learn more filoviruses.
Principal investigator Lijun Rong, a professor in microbiology and immunology, notes that: “We know very little about the basic biology of these diseases.”
In their study, he and his colleagues discovered that the way Ebola and Marburg gain entry into host cells – where they take over cell machinery to make copies of themselves – is via a cell surface receptor that acts like a gateway.
The cell surface receptor is a type of protein called a GPCR (G protein-coupled receptor). GPCRs sit on the surface of cells and are involved in a broad range of biological processes. A large number of clinically used drugs act through these gateway proteins.
Prof. Rong explains there are probably more than a thousand different GPCRs in humans that are involved in many diseases, so a large number of drugs has already been developed to target them. He adds:
“In the history of therapeutics, about half of our drugs were developed to target GPCRs. For example, a number of antihistamines used as allergy medications are GPCR receptor antagonists.”
The team screened around 1,000 compounds and found that 20 GPCR antagonists – molecules that block the receptor – were able to stop Ebola and Marburg viruses from entering host cells.
The researchers say their findings “strongly suggest that GPCRs play a critical role in filoviral entry” and that GPCR antagonists can be developed as an effective therapy against Ebola and Marburg viruses.
Prof. Rong says there are a lot of drugs that work through this mechanism and concludes:
“This gives us a huge repertoire that can be tested against Ebola/Marburg.”
Meanwhile, MNT learned recently how another team has discovered another two protein pathways critical to Ebola can be blocked, and that there are also drugs currently in use that target these pathways, which are called PI3 kinase and CAMK2.