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'Broad spectrum' antiviral fights multitude of viruses

Date:
February 2, 2010
Source:
University of Texas Medical Branch at Galveston
Summary:
Researchers are developing and testing a broad-spectrum antiviral compound capable of stopping a wide range of highly dangerous viruses, including Ebola, HIV, hepatitis C virus, West Nile virus, Rift Valley fever virus and yellow fever virus, among others.

Ebola virus. A small-molecule "broad spectrum" antiviral may be able to fight a host of viruses by attacking them through some feature common to an entire class of viruses.
Credit: Frederick Murphy

The development of antibiotics gave physicians seemingly miraculous weapons against infectious disease. Effective cures for terrible afflictions like pneumonia, syphilis and tuberculosis were suddenly at hand. Moreover, many of the drugs that made them possible were versatile enough to knock out a wide range of deadly bacterial threats.

Unfortunately, antibiotics have a fundamental limitation: They're useless against viruses, which cause most infectious diseases. Antiviral drugs have proven far more difficult to create, and almost all are specifically directed at a few particular pathogens -- namely HIV, herpes viruses and influenza viruses. The two "broad-spectrum" antivirals in use, ribavirin and interferon-alpha, both cause debilitating side effects.

Now, researchers from the University of Texas Medical Branch at Galveston, UCLA, Harvard University, the U.S. Army Medical Research Institute of Infectious Diseases and Cornell University have teamed up to develop and test a broad-spectrum antiviral compound capable of stopping a wide range of highly dangerous viruses, including Ebola, HIV, hepatitis C virus, West Nile virus, Rift Valley fever virus and yellow fever virus, among others.

UCLA researchers led by Dr. Benhur Lee -- corresponding author on a paper on the work appearing in the Proceedings of the National Academy of Science -- identified the compound (which they call LJ001), after screening a "library" of about 30,000 molecules to find a one that blocked the host cell entry of deadly Nipah virus. Subsequent experiments revealed that LJ001 blocked other viruses that, like Nipah, were surrounded by fatty capsules known as lipid envelopes. It had no effect on nonenveloped viruses.

"Once we started testing more and more, we realized that it was only targeting enveloped viruses," said Alexander Freiberg, director of UTMB's Robert E. Shope, M.D. Laboratory, the Biosafety Level 4 lab where much of the cell-culture work was done, as well as mouse studies with Ebola and Rift Valley fever viruses. "We followed up and determined that it was somehow changing the lipid envelope to prevent the fusion of the virus particle with the host cell."

Additional experiments indicated that while LJ001 also interacted with cell membranes, whose composition is nearly identical with that of virus envelopes, it caused them no ill effects. The reason, according to the researchers: Cells can rapidly repair their membranes, but viruses can't fix their envelopes.

"At antiviral concentrations, any damage it does to the cell's membrane can be repaired, while damage done to static viral envelopes, which have no inherent regenerative capacity, is permanent and irreversible," said Lee.

UTMB authors of the PNAS paper include graduate student Sara Woodson and adjunct associate professor Michael Holbrook, former director of the Shope BSL4 lab and principal investigator on the UTMB portion of the project. UCLA contributors are Mike Wolf, Tinghu Zhang, Zeynep Akyol-Ataman, Andrew Grock, Patrick Hong, Natalya Watson, Angela Fang, Hector Aguilar, Robert Damaoiseaux, John Miller, Steven Chantasirivisal, Vanessa Fontanes, Oscar Negrete, Paul Krogstad, Asim Dasgupta, Kym Faull and Michael Jung. Other authors are Jianrong Li and Sean Whelan of Harvard; Matteo Porotto and Anne Moscona of Cornell; and Anna Honko and Lisa Hensley of USAMRIID.


Story Source:

The above story is based on materials provided by University of Texas Medical Branch at Galveston. Note: Materials may be edited for content and length.


Journal Reference:

  1. Wolf et al. A broad-spectrum antiviral targeting entry of enveloped viruses. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.0909587107

Cite This Page:

University of Texas Medical Branch at Galveston. "'Broad spectrum' antiviral fights multitude of viruses." ScienceDaily. ScienceDaily, 2 February 2010. <www.sciencedaily.com/releases/2010/02/100201113801.htm>.
University of Texas Medical Branch at Galveston. (2010, February 2). 'Broad spectrum' antiviral fights multitude of viruses. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2010/02/100201113801.htm
University of Texas Medical Branch at Galveston. "'Broad spectrum' antiviral fights multitude of viruses." ScienceDaily. www.sciencedaily.com/releases/2010/02/100201113801.htm (accessed July 31, 2014).

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