Developed at UC San Diego more than a decade ago, brincidofovir takes on Ebola.
With the Ebola crisis ongoing, much attention is focused upon finding a drug capable of slowing – if not stopping – the infectious, deadly and terrifying virus.
There is Zmapp, of course, the experimental biopharmaceutical produced by a San Diego-based biotech firm that was used briefly before supplies ran out. There are other anti-Ebola drugs reportedly under development in Oregon, Canada and China.
And there is brincidofovir, a compound with a decidedly unwieldy name that was discovered more than a decade ago by researchers at UC San Diego. Brincidofovir (pronounced brin-SIGH-doh-fo-veer) wasn’t invented to fight Ebola – the scientists were actually looking for a new way to fend off the menace of bioterrorism – but it may represent one of the best chances yet to conquer a virus that has killed more than 4,500 people, almost all in stricken West Africa.
In 1999, Dr. Karl Hostetler, then a professor of medicine in UC San Diego School of Medicine, got a call from officials at the National Institute of Allergy and Infectious Diseases. They posed a question: Could he help create a new drug to protect Americans if bioterrorists unleashed smallpox – the one-time global scourge now restricted to a few high-security labs?
There was already a drug called cidofovir that might serve, but it required an injection. NIAID officials wanted a pill, something safe, stable and broadly effective against not just smallpox, but other highly infectious, deadly viruses that might be deployed as bioweapons.
“There was a lot of talk and fear about such attacks at the time,” recalled Hostetler, now professor emeritus. “It’s still a legitimate concern.”
Hostetler, who studied the lipid molecules necessary to build cell membranes and was working on improved ways to deliver therapeutic drugs inside cells, agreed to help. Funding from NIAID arrived within days.
Over the next few years, he and colleagues created multiple analogs or variations of cidofovir. The first was brincidofovir. In cultured cell tests, the compound proved active against an array of viruses, blocking their ability to replicate.
“With any disease that causes high mortality, the idea isn’t so much to absolutely stop viral replication as to slow it down so that the patient’s immune system can catch up and ultimately eradicate the infection,” Hostetler said.
One of the viruses seemingly impacted by brincidofovir is Ebola, though Hostetler’s focus at the time was elsewhere. Brincidofovir targets double-stranded DNA viruses like herpes, cytomegalovirus, Epstein-Barr, hepatitis and papillomavirus. Ebola is an RNA virus. It replicates differently.
“Brincidofovir is the first broad-spectrum antiviral for DNA viruses. It’s not unprecedented that it might also work against RNA viruses like Ebola, but back then, the greatest interest was in DNA viruses,” he said.
Unable to arouse outside interest and investment in brincidofovir, Hostetler founded Chimerix in Durham, N.C. to further develop the drug – both for smallpox and for other diseases. These efforts have progressed measurably. Phase 3 trials under the Food and Drug Administration’s (FDA) animal rule are planned next year for a smallpox treatment. Phase three human trials are underway for brincidofovir as a therapy for cytomegalovirus and adenovirus – common viruses that can cause fever, diarrhea, conjunctivitis and bladder infections, but in persons with weakened or suppressed immune systems are life-threatening.