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The Cutting Edge

Antiviral Assault Gains Ground

MedMagSpring10-Virus EntryA NATIONAL GROUP OF RESEARCHERS led by a team from UCLA may have found a broad-spectrum antiviral that will fight a host of viruses by attacking them through some feature that is common to an entire class of viruses, without producing unwanted side effects.

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.

U.S. Food and Drug Administration-approved broad-spectrum antivirals do exist but are rare, for various reasons. They are effective against only a limited number of viruses, for example, or they have unwanted side effects or are too expensive for widespread use. But the putative mechanism for LJ001 is surprising, says Benhur Lee, M.D., associate professor of microbiology, immunology and molecular genetics. “We provide evidence that the small molecule binds to both cellular and viral membranes, but its preferential ability to inactivate viral membranes comes from its ability to exploit the biogenic reparative ability of metabolically active cells versus static viral membranes,” he says. “That is, at antiviral concentrations, any damage it does to the cell’s membrane can be repaired, while damage done to static viral membranes, which have no inherent regenerative capacity, is permanent and irreversible.”

While the exact mechanism of viral membrane inactivation is unknown, the researchers – including scientists from the University of Texas at Galveston, Harvard University, Cornell University and the United States Army Medical Research Institute of Infectious Diseases – are pursuing some promising leads that could answer that question.

 





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