Tag: Marburg

The Ebola Relative, Lloviu Virus, Has Pandemic Potential

Photo by Todd Cravens on Unsplash

Researchers have helped isolate the Lloviu virus (LLOV), a close relative of Ebola virus, for the first time, showing that it could cross over into humans, highlighting the need for future research to ensure pandemic preparedness. The study is reported in Nature Communications.

LLOV is part of the filovirus family, which also includes the Ebola virus. While Ebola (and other filoviruses including the lethal Marburg virus) have only occurred naturally in Africa, Lloviu has been discovered in Europe. The filovirus LLOV, was genetically identified in 2002 in Schreiber’s bats in Spain and was subsequently detected in bats in Hungary.

As a zoonotic virus, LLOV is of public health interest to public health around the world due to our close relationship with animals in agriculture, as companions and in the natural environment. Increasing encroachment on the natural environment is creating more opportunities for zoonotic viruses to cross over into humans.

Dr Simon Scott, from the Viral Pseudotye Unit (VPU) at Medway School of Pharmacy were part of a team led by Dr Gábor Kemenesi from Pécs University/National Laboratory of Virology in Hungary. The VPU were involved in conducting all the antibody detection experiments using bat sera as part of the study, even before the virus itself was isolated. This isolation occurred in the Hungarian lab from the very last bat which tested LLOV positive.

The team discovered that Lloviu has the potential to both infect human cells and replicate, raising concerns about potential widespread transmission in Europe and urges immediate pathogenicity and antiviral studies. The VPU work also revealed no antibody cross-reactivity between LLOV and Ebola, suggesting that existing Ebola vaccines might not protect against Lloviu.

Dr Scott said that their research “is a smoking gun. It’s vital that we know both more about the distribution of this virus and that research is done in this area to assess the risks and to ensure we are prepared for potential epidemics and pandemics.”

The research revealed a considerable knowledge gap regarding the pathogenicity, animal hosts, and transmissibility of these newly discovered viruses. Dr Scott created a consortium of European bat virologists, harnessing expertise in the field, from ecology to virology, which is aiming to carry out essential further research across Europe into the risks of the Lloviu virus to humans.

Source: University of Kent

Marburg Virus Detected in Guinea

Colourised scanning electron micrograph of Marburg virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (orange). Credit: NIAID

Guinea’s health authority announced the first detection of the Marburg virus in the country, which is also the first case in West Africa.

Marburg, a haemorrhagic fever-causing virus related to Ebola, killed more than 200 people in Angola in 2005, the deadliest recorded outbreak. Laboratory tests of samples taken from a now-deceased patient turned out positive for the Marburg virus.

The patient had sought treatment at a local clinic in the southern prefecture of Gueckedou, and a medical team had been sent to investigate the case.  Cases of the 2021 Ebola outbreak in Guinea occurred in Gueckedou, as well as the 2014–2016 West Africa outbreak were initially detected.

“We applaud the alertness and the quick investigative action by Guinea’s health workers. The potential for the Marburg virus to spread far and wide means we need to stop it in its tracks,” said Dr Matshidiso Moeti, World Health Organization (WHO) Regional Director for Africa. “We are working with the health authorities to implement a swift response that builds on Guinea’s past experience and expertise in managing Ebola, which is transmitted in a similar way.”

Contact tracing efforts are underway, and health authorities are launching education and awareness programmes on the disease. 

Four high-risk contacts, including a healthcare worker, have been identified, as well as 146 others who could be at risk, according to expert Dr Krutika Kuppalli, who spoke to the BBC. A team of WHO experts is on the ground helping to investigate the case and aiding the national health authority’s emergency response.

Cross-border surveillance is also being enhanced to quickly detect any cases, with neighbouring countries on alert. The Ebola control systems in place in Guinea and in neighbouring countries are proving crucial to the emergency response to the Marburg virus.

Marburg is transmitted to people from fruit bats and spreads among humans through direct contact of body fluids.

Illness begins abruptly, with high fever, severe headache and malaise. Within seven days, severe haemorrhagic signs appear in many patients. Case fatality rates are high, ranging from 24% to 88% in past outbreaks depending on virus strain and case management.

With no direct treatments for the virus, supportive care, including rehydration with oral or intravenous fluids, and treatment of specific symptoms, improves survival. There are evaluations underway for potential treatments, including blood products, immune therapies and drug therapies.

One experimental antiviral compound being tested works by preventing viral particles from ‘budding off’ of infected cells.

Source: WHO

Experimental Inhibitor Drug Shows Promise For The Deadly Marburg Virus

Photo by CDC on Unsplash

The lethal Marburg virus, a relative of the Ebola virus, causes a serious haemorrhagic fever with an extremely high fatality rate and has had no known treatment — until now. 

Marburg virus infects human and primates, the disease currently has no approved vaccine or antivirals for prevention or treatment. In two larger recent outbreaks in the DRC in 1998–2000, and in Angola in 2004–2005, Marburg had extremely high fatality rates of 83% and 90%.

A team of researchers is working to change that. In a new paper in the journal Antimicrobial Agents and Chemotherapy, investigators from Penn’s School of Veterinary Medicine, working together with scientists from the Fox Chase Chemical Diversity Center and the Texas Biomedical Research Institute, report encouraging results from tests of an experimental antiviral targeting Marburg virus.

The new compound prevents viruses from leaving infected cells, thus halting the spread of infection. In a first, this new class of inhibitors was shown to be effective against infection in an animal model.

Additionally, possible similarities in virus-host interactions between Marburg and SARS-CoV-2, prompted the team to conducted experiments on the coronavirus. Unpublished preliminary results appeared encouraging.

“It really is exciting. These viruses are quite different but may be interacting with the same host proteins to control efficient egress and spread, so our inhibitors may be able to block them both,” said co-corresponding author Ronald Harty, Professor, Penn’s School of Veterinary Medicine.

Prof Harty’s team have been developing an antiviral that instead of targeting the virus known as “host-oriented.” By blocking the proteins in host cells that viruses hijack during late stages of infection, preventing virus-host interactions.

This method helps prevent a virus evolving resistance, but it also makes it more likely that a drug could be used against multiple viruses, as many make use of the same machinery in the host cell to reproduce and spread.

The Marburg and Ebola viruses use protein known as VP40 to interact with a host protein called Nedd4 to allow the completed viruses to ‘bud off’ of the host cell, which is a key part of viral replication.

Previously, they had tested a variety of small molecule inhibitors of this process using laboratory tests that relied on non-infectious and more-benign viral models. Those assays led them to a promising candidate, FC-10696, for further study.

The researchers firstly tested the chosen inhibitor for safety and its useful duration within the body. Next, since the real Marburg virus is too dangerous to study safely in anything but a Biosafety Level 4 (BSL-4) laboratory, they used an assay to look at what are known as virus-like particles, or VLPs, which are non-infectious but can bud off of a host cell.

Using the Biosafety Level 2 laboratory at Penn, “it’s a very quick way we can test these inhibitors,” said Prof Harty.

The researchers saw a dose-dependent response to FC-10696 on VLP budding in cells tested the compound using the real Marburg virus. These studies were done in a BSL-4 lab at Texas Biomedical Research Institute and found the compound inhibited the budding and spread of live Marburg virus in two human cell types, including in macrophages, an immune cell type commonly infected by the virus.

As a final step, they tested the compound in mice infected with Marburg virus. That received the treatment took longer to display disease symptoms and had a reduced viral load.

“These are the first promising in vivo data for our compounds,” said Prof Harty. “Whereas the control group all became sick very quickly and died, with the treated animals there was one survivor and others showed delayed onset of clinical symptoms. It’s showing that our inhibitors are having an effect.”

Source: News-Medical.Net

Journal information: Han, Z., et al. (2021) Compound FC-10696 Inhibits Egress of Marburg Virus. Antimicrobial Agents and Chemotherapy. doi.org/10.1128/AAC.00086-21.