Virus World

A drug studied for cancer, COVID-19 and radiation injuries appears to be effective against Ebola in mice. | From cancer to COVID-19 to radiation injuries, and now Ebola: RedHill Bio reports that its drug opaganib appears to be effective against the virus in mice. RedHill Biopharma, in collaboration with the U.S. Army, announced Oct. 3 that twice-daily oral doses of the medication opaganib boosted survival from about six days in controls to 11 days in animals infected with the virus. In the group treated with the highest dose, 30% of the mice survived, compared to none of the controls. “Given the unmet medical need … these results with opaganib, an easy to distribute and administer oral small molecule drug, support its further investigation for use in treating Ebola,” study lead Rekha Panchal, Ph.D., principal investigator of therapeutics discovery at the U.S. Army Medical Research Institute of Infectious Diseases, said in a press release.

Opaganib is a host-directed antiviral, meaning it prevents a virus from hijacking a host’s cells for replication rather than destroying the pathogen directly. The drug mainly works by inhibiting the enzyme sphingosine kinase-2, or SPHK2, a key enzyme in a process called sphingolipid metabolism. Inhibiting sphingolipid metabolism with opaganib turns on processes that clear or repair infected cells, like autophagy and apoptosis. That mechanism has prompted studies on opaganib in a range of indications from cancer to COVID. Under the name Yeliva, the drug received orphan-drug designation from the FDA in 2017 for the treatment of bile duct cancer and has been tested for that indication through phase 2a. It’s also in a phase 2 study for prostate cancer. In 2021, the drug flopped in a phase 2/3 test on patients with severe COVID-19 pneumonia, though RedHill said at the time it would continue investigating the drug in patients who were earlier in the course of their disease.

In February 2023, opaganib was selected for investigation by the National Institutes of Health and the Radiation and Nuclear Countermeasures Program as a potential treatment for acute radiation syndrome. The move came on the back of preclinical studies in mice suggesting it could prevent damage from ionizing radiation. If the drug were to show efficacy against Ebola in humans, it would be only the third to do so. The two FDA-approved treatments for the virus both rely on antibodies that prevent it from entering the host’s cells and must be given by IV.

Red Hill Biopharma Press Release (Oct. 3, 2023):

https://www.redhillbio.com/news/news-details/2023/RedHill-and-U.S.-Army-Announce-Opaganibs-Ebola-Virus-Disease-Survival-Benefit-in-U.S.-Army-Funded-In-Vivo-Study/default.aspx 

It is now more than four decades since Professor Peter Piot sped from a clinical lab in the bustling Belgian city of Antwerp to a remote rainforest in the heart of Africa to investigate a mysterious epidemic. 

Three weeks earlier the microbiology lab where the then 27-year-old worked had received two vials of blood  transported halfway across the globe in a cheap blue thermos flask filled with ice. One of the test tubes had smashed, but at the time in 1976 Prof Piot and his colleagues were unaware of the danger lurking inside. The two vials contained a new but highly contagious virus which we now know as Ebola – a disease which has killed more than 2,000 people in a 13-month outbreak in the Democratic Republic of Congo (DRC). The blood samples were from Flemish nuns living in what was then known as Zaire, who had died of a mysterious haemorrhagic fever. Within three weeks the virus had killed 200 people in Yambuku, a small village in the Congolese forest home to a Belgian missionary outpost.  

“The discovery itself was an accident, or a coincidence,” Prof Piot says, sitting in his directors' office at the London School of Hygiene Tropical Medicine, which celebrated its 120th anniversary this autumn .  “We obviously did not know there was Ebola in the samples from Zaire. Looking back, probably the most dangerous moments were working in the lab in Antwerp.”

It wasn’t long before the team, examining the virus’ gigantic worm structure under a microscope, realised this was a new disease and sent the samples to the specialist Centre for Disease Control in the US for confirmation. Within weeks Prof Piot was on a flight – without so much as a valid passport. “I’m trying not to exaggerate, but in less than 48 hours I went from Antwerp to the tropical rainforest in northern Zaire,” he says. “It was extremely exciting, to be honest.”  

“I’d never been to Africa, I’d never investigated an epidemic, so I definitely did not qualify and in today’s world, I don’t think I would be allowed to do this.”

As Prof Piot recalls in his book, No Time to Lose, what followed were two adventure-filled but exhausting months, predominantly spent in the jungle some 600 miles from Zaire’s capital city, Kinshasa. An international team of scientists meticulously investigated the disease, which slowly petered out after killing 280 people......