Compound could be used against HIV-1, Nipah, Ebola and other deadly viruses
Viruses are insidious creatures. They differ from each other in many ways, and they can mutate - at times seemingly at will, as with HIV - to resist a host of weapons fired at them. Complicating matters further is that new viruses are constantly emerging.
One potential weapon is a small-molecule "broad spectrum" antiviral that will fight a host of viruses by attacking them through some feature common to an entire class of viruses. For example, there are two categories of viruses: lipid-enveloped and non-enveloped. Enveloped viruses are surrounded by a membrane that in effect serves as a mechanism through which a virus inserts its genome into a host cell, infecting it. Is there something out there that might disrupt that action in as many viruses as possible - and not produce unwanted side effects?
A group of researchers led by a team from UCLA and including others from the University of Texas at Galveston, Harvard University, Cornell University and the United States Army Medical Research Institute of Infectious Diseases may have found just such a compound.
In a proof-of-principle study published online in Proceedings of the National Academy of Sciences, the researchers have identified an antiviral small molecule that is effective against numerous viruses, including HIV-1, influenza A, filoviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses and flaviviruses. These viruses cause some of the world's deadliest diseases, such as AIDS, Nipah virus encephalitis, Ebola, hemorrhagic fever and Rift Valley fever.
Even better, the compound - a rhodanine derivative that the researchers have dubbed LJ001 - could be effective against new, yet-to-be discovered enveloped viruses.
"Since the government has changed its priorities to support development of broad spectrum therapeutics, more and more groups have been screening compound libraries for antivirals that are active against multiple viruses in a specific class," said Dr. Benhur Lee, associate professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA and the primary investigator of the four-year study.
U.S. Food and Drug Administration-approved broad spectrum antivirals do exist but are rare, for various reasons. Ribavirin, for instance, affects both the virus proteins and the host cell and is effective on only a limited number of viruses, such as respiratory syncytial virus and Lassa fever virus. And α-interferon, which is used against the hepatitis C virus, produces unwanted side effects and is too expensive for widespread use.
But the putative mechanism for LJ001 is surprising, according to Lee, who is also a member of the UCLA AIDS Institute.