Virus-directed drugs tend to become less effective over time as the constantly mutating virus develops resistance to the drug, Dr. Reinherz explains. "The advantage of targeting signaling pathways is that cells--and the structures that send and receive signals--are far less likely to mutate than viruses themselves, making it improbable that drugs will lose their potency," he says.
The new findings build on earlier work by the researchers in which they determined that smallpox growth factor (SPGF), a protein produced by the smallpox virus, attaches to a cell membrane receptor called erb-B1. This interaction primes the cell to become a factory for producing new virus particles.
Could smallpox replication be hampered by specifically blocking the SPGF pathway? To find out, Dr. Reinherz and his team added an experimental drug, CI-1033, to monkey kidney cells that had been infected with smallpox virus. CI-1033, which is being developed by Pfizer Corporation as a potential cancer treatment, halts erb-B1's function. The investigators found that production of new virus particles and spread of the virus to uninfected cells was significantly impaired when erb-B1-blocking CI-1033 was present.
In other experiments, the researchers found that CI-1033, used preventively, offered significant protection from serious illness in mice infected with a relative of the smallpox virus. Mice receiving both CI-1033 and a single dose of an infection-fighting antibody completely cleared the virus from their lungs within eight days of the initial infection.
The researchers are searching fo
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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
1-Feb-2005