Benhur Lee may have discovered a medical silver bullet—one that can disable HIV, the exotic Ebola virus, the common flu and possibly every kind of enveloped virus on the planet.
Working from his laboratory at the University of California, Los Angeles, Lee came across this bullet after first creating a hybrid virus, one that combined the envelope (or outer surface) of the deadly Nipah virus and the core of the benign vesicular stomatitis virus. The hybrid can infect cells but cannot replicate in them.
He then screened a library of 30,000 compounds for activity against the hybrid’s envelope to see if they inhibited entry into the cell. One compound, called LJ001, “looked really good,” Lee recalls, and it wasn’t toxic to cell cultures.
After a series of studies confirmed the activity and lack of toxicity, Lee sent samples of the compound to the Galveston National Laboratory at the University of Texas Medical Branch, which has biosafety labs for testing against whole Nipah, Ebola and other deadly viruses. Amazingly, LJ001 inhibited viral entry of all of them. Lee later pitted it against HIV—it worked there, too. He continued testing the compound against more viruses until the list reached 20—all successes.
Additional experiments revealed that the compound failed against an entirely different class of viruses. At that point, Lee figured out LJ100’s secret: it works only against viruses that have lipid envelopes, which also happen to be the most deadly ones.
The compound evidently binds to lipids in the envelope of both the virus and human cells, causing damage to both. The difference is that the cell can repair all kinds of regularly occurring insults; the genetically simpler virus has no repair mechanisms. (Newly created viruses get their lipid coats by literally ripping them off the cell membrane as they bud from infected cells.) Once the viral lipids were disabled by LJ001, they stayed that way. Lee’s first paper on the compound’s antiviral activity appeared in the February 16 Proceedings of the National Academy of Sciences USA.
Virologist Warner C. Greene of the University of California, San Francisco, finds the work fascinating but cautions that “from a therapeutic point of view, it is a very, very early finding.” He notes that the membrane disruption may be more toxic than is currently appreciated. “Primary cells often are much more sensitive than laboratory-adapted cells,” Greene says.
Lee certainly hopes to find out. He is currently working with others at U.C.L.A. to turn the promising compound into an actual drug, which would have more going for it than just a broad-spectrum ability. “I can’t imagine how the virus can develop resistance to this type of drug,” Lee says.
This article was originally published with the title Bad Wraps on Viruses.