Highly pathogenic RNA viral infections: challenges for antiviral research

A number of RNA viruses can cause severe disease when transmitted to humans from an animal reservoir. One of them, the recently emerged H5N1 subtype of influenza A virus, has caused several hundred cases of severe disease when transferred directly from domestic poultry. This or another avian subtype could potentially evolve to a form more transmissible by the respiratory route or reassort with a circulating strain to initiate a pandemic. Other zoonotic RNA viruses cause sporadic single cases or outbreaks of hemorrhagic fever or encephalitis that spread inefficiently from person-to-person, and thus remain confined to the geographic range of the maintenance host. RNA viral infections of farm animals, such as foot and mouth disease and classical swine fever, also pose a major threat to human well-being through economic loss and impaired nutrition. Only a few licensed antiviral drugs are available to prevent or treat these conditions. Medications that inhibit the replication of influenza virus might be used in an epidemic both to treat severe disease and to block the spread of infection. The guanosine analog ribavirin has been used to treat a few types of hemorrhagic fever, but there is no specific therapy for the others, or for any type of RNA viral encephalitis. The quest for new antivirals is being supported by government programs and new collaborative research networks. Major efforts will be required to identify active compounds, test their efficacy in laboratory animals, obtain approval for human use and develop rapid diagnostic methods that can identify patients early enough in the disease course for treatment to be of benefit.