The potential use of smallpox virus as a bioterror agent and the endemic presence of monkeypox virus in Africa underscores the need for better
therapies for
orthopoxvirus infections. The only existing clinical experience treating
vaccinia and
smallpox infections has been with
Marboran, which suggested that
antiviral therapies could be effective in treating and preventing
smallpox infections, but this compound has not been pursued. Drugs that have been approved for other indications, like
cidofovir, could be approved for the treatment of
orthopoxvirus infections in a timely manner, and this compound has already been approved for
emergency treatment of
smallpox and complications from vaccination. Its lack of activity when given orally, however, limits its use in a major outbreak involving large numbers of people exposed to the virus. The discovery and development of new
therapies can be achieved more rapidly by drawing on the experience and successes with other
antiviral agents, particularly with the herpesviruses. This review will discuss the orthopoxvirus replication cycle in detail noting specific viral functions and their associated gene products that have the potential to serve as new targets for
drug design and development. This discussion is designed to help investigators relate these targets to parallel functions and existing assays in other virus systems that have been used successfully in
drug development. The rapid progress that has been achieved in recent years should yield new drugs for the treatment of these
infections and might also reveal new strategies for
antiviral therapy with other viruses.