Discovery of antivirals against smallpox
- Stephen C. Harrisona,b,
- Bruce Albertsc,
- Ellie Ehrenfeldd,
- Lynn Enquiste,
- Harvey Finebergf,
- Steven L. McKnightg,
- Bernard Mossh,
- Michael O'Donnelli,
- Hidde Ploeghj,
- Sandra L. Schmidk,
- K. Peter Walterl, and
- Julie Theriotm
- aHarvard Medical School, Howard Hughes Medical Institute, Seeley Mudd Building, Room 130, 250 Longwood Avenue, Boston, MA 02115;cNational Academy of Sciences, 2101 Constitution Avenue, NW, Washington, DC 20418;dLaboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 50, Room 6120, 50 South Drive, Bethesda, MD 20892;ePrinceton University, 314 Schultz Laboratory, Washington Road, Princeton, NJ 08544;fInstitute of Medicine, 2101 Constitution Avenue, NW, Washington, DC 20418;gDepartment of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390;hLaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 229, 4 Center Drive, Bethesda, MD 20892;iLaboratory of DNA Replication, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10021;jDepartment of Pathology, Harvard Medical School, NRB, 77 Avenue Louis Pasteur, Boston, MA 02115;kDepartment of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037;lDepartment of Biochemistry and Biophysics, University of California School of Medicine, Howard Hughes Medical Institute, Box 0448, HSE 1001, San Francisco, CA 94143; andmDepartment of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305
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Contributed by Stephen C. Harrison, May 21, 2004
Smallpox, a devastating infectious disease dreaded throughout much of recorded history, is caused by the variola virus, a member of the poxviridae family. In the 20th century alone, smallpox deaths worldwide numbered in the millions. In 1980, after an intensive program of immunization with vaccinia virus, a related but relatively nonpathogenic virus, the World Health Organization (WHO) declared the disease eradicated. By 1983, all known stocks of variola virus were in two WHO collaborating centers: the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta and (after a transfer in 1994) the Russian State Research Center of Virology and Biotechnology (the Vektor Institute) in Novosibirsk. The WHO Committee on Orthopoxvirus Infections voted on several occasions to recommend destruction of the stocks, but each time the decision was deferred to permit more research on live variola virus. A 1999 National Academies report summarized and assessed scientific needs for live variola virus (1).
The concern that undeclared stocks of variola virus might exist and that they might be used as a bioterrorist weapon (2) was heightened in late 2001 by the deliberate release of Bacillus anthracis, the agent of anthrax, in the weeks after the September 11, 2001, attacks. That concern prompted a voluntary national-preparedness effort to vaccinate healthcare workers, first responders, and members of the military against smallpox. However, given the substantial side effects, the risks associated with the smallpox vaccine, and the absence of information about an imminent bioterrorist attack, vaccination was not accepted by all members of those groups, nor was it recommended for the general public by the government (3).
Whatever the likelihood of covertly held variola virus stocks, an intentional release of the virus would pose a serious health threat and would probably provoke a …
