A group of NIAID-supported researchers led by Dr. Benhur Lee and his team at the University of California, Los Angeles (UCLA), has identified a small-molecule “broad spectrum” antiviral that is effective fighting multiple deadly viruses, including HIV-1, Ebola, Rift Valley fever, and Nipah. The compound—a rhodanine derivative that researchers have named LJ001—could also be effective against emerging viruses that have yet to be identified.
Viruses can be divided generally into two main categories: lipid-enveloped and non-enveloped. A lipid-enveloped virus uses its surrounding membrane to transport its genome into the next target host cell, thereby infecting it. In a study published online in Proceedings of the National Academy of Sciences, the researchers describe how LJ001 inhibited entry, or infectious spread, of a wide variety of enveloped viruses, and a large number of highly virulent pathogens, without affecting non-enveloped viruses. Despite different target cell types, viruses, and measures of infectivity, LJ001 demonstrated roughly similar success among the enveloped viruses tested. These results suggest that the antiviral likely targets a component common to the entire class of enveloped viruses. There are few known broad-spectrum antiviral and even fewer that are approved. Those few have serious deficiencies. Ribavirin, for example, affects both the virus proteins and the host cell but is effective on only a limited numbers of viruses.
Researchers identified LJ001 after screening about 30,000 molecules to find one that blocked the entry of the deadly Nipah virus into a host cell. Subsequent experiments revealed that LJ001 also blocked other lipid-enveloped viruses. The antiviral changed the lipid-envelope to prevent the fusion of the virus particle with the host cell. It had no effect on non-enveloped viruses as well as the host cell that is the target of the enveloped virus. Researchers say that is because a cell can rapidly repair the damage done to its membrane by the compound, while a virus cannot.
The rapid rise in the number of emerging viral pathogens underscores the need to develop broad spectrum antivirals that target common components of large classes of viruses. NIAID is leading the science in this area in a way that private sector groups haven’t done. The discovery of LJ001 by a collaborative, multidisciplinary team of NIAID-supported researchers was funded using multiple NIAID resources. It is a strong example of how the Institute explores different funding mechanisms and builds relationships across sectors that lead to this kind of science advance—one that has positive, potentially far-reaching implications for therapeutics for emerging viruses.
In addition to UCLA, the team also included researchers at the University of Texas Medical Branch at Galveston, Harvard University, Cornell University, the Center for AIDS Research at UCLA, and the United States Army Medical Research Institute of Infectious Diseases.
Wolf MC et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proceedings of the National Academy of Sciences. DOI: 10.1073/PNAS0909587107.
back to top
Last Updated May 05, 2010