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New Approach to Anti-Viral Therapy May Help Overcome Drug Resistance

Anti-Protease Approach

Because proteases are so prevalent in infections caused by viruses and bacteria, Mangel suggests that multiple drug treatments against proteases might be effective in treating a wide variety of ailments, including those caused by hepatitis virus, herpes virus, polio virus, dengue virus, SARS virus, and bacterial diseases such as Chlamydia and plague. In fact, Mangel has recently expanded his work to develop anti-viral agents for use against the coronavirus which causes SARS, or severe acute respiratory syndrome, which was first reported in Asia in 2003. Eventually, he wants to apply the technology developed in his lab to combating malaria, the parasite-caused illness that strikes 300-500 million people worldwide, causes about 1,200 cases in the U.S., and results in the death of 1 million people each year.

'Atomic Biology'

Mangel says: “The golden age of biology will peak in this century, especially at places like Brookhaven Lab, where biologists collaborate easily with physicists, chemists, and computer scientists to work on complex problems. For the last 50 years, molecular biology, a combination of biochemistry and genetics, was the major discipline in biology. Now, a new discipline is emerging — atomic biology — which is a combination of structural biology and molecular biology. Our ability to define biological molecules and the processes they undertake atom by atom using facilities like the NSLS will produce a new level of understanding of the relationship between structure and function in biology — and, ultimately, the ability to predict structures and functions. And this will lead to effective drugs against viruses, bacteria, and, possibly, even malaria.”

Meet Walter Mangel

Walter Mangel

Walter Mangel likens protein-cleaving by viral proteases — the enzymes that he is studying in the quest for a new form of anti-viral therapy — to the final step in cathedral construction: As are viruses, cathedrals are built around an internal scaffold, which has to be removed for the final product to be functional.

Mangel’s analogy is not surprising given his interest in the arts. With a B.S. in philosophy and a Ph.D. in biophysics from the University of Illinois, Urbana, he blends science and art whenever he can. For instance, during a recent presentation on his virus studies, he concluded with drawings that he made of the people in his lab — artwork that will be on display at a Long Island gallery this summer.

Before coming to Brookhaven in 1985, Mangel did postdoctoral research at the University of California, Berkeley, and the Imperial Cancer Research Fund Laboratory in London, England. At Brookhaven, he has been working on virus-coded proteases, malaria, and SARS. Aware of the insightful power of structural biology, Mangel has, for the last seven years, been using the x-ray crystallography stations at the National Synchrotron Light Source.

As much as he enjoys literature, Mangel’s greatest passion is classical music and opera. As he explains, “My enjoyment in listening to great music and in doing science is similar.”

More Information

  • Research funding: National Institutes of Health; Office of Biological & Environmental Research, Office of Science, U.S. Department of Energy
  • Paper: “A new form of antiviral combination therapy predicted to prevent resistance from arising, and a model system to test it.” W.F. Mangel et al., 2001, Current Medicinal Chemistry, vol. 8., pp. 933-939
  • Contacts: Walter Mangel, , (631) 344-3373
  • Web:
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