Orthopoxvirus Inhibitors that are Active in Animal Models: An Update from 2008 to 2012

Abstract

Antiviral agents are being sought as countermeasures for the potential deliberate release of smallpox (variola) and monkeypox viruses, for the treatment of naturally acquired monkeypox virus infections, and as therapy for complications due to smallpox (live-attenuated vaccinia virus) vaccination or accidental infection after exposure to vaccinated persons. Reviews of the scientific literature spanning 1950–2008 have documented the progress made in developing small-animal models of poxvirus infection and identifying novel antiviral agents. Compounds of considerable interest include cidofovir, CMX001 and ST-246^® (tecovirimat; SIGA Technologies, NY, USA). New inhibitors have been identified since 2008, most of which do not exhibit the kind of potency and selectivity required for drug development. Two promising agents include 4´-thio-idoxuridine (a nucleoside analog) and mDEF201 (an adenovirus-vectored interferon). Compounds that have been effectively used in combination studies include vaccinia immune globulin, cidofovir, ST-246 and CMX001. In the future there may be an increase in experimental work using active compounds in combination.

Keywords:

• antiviral
• camelpox
• cowpox
• drug combinations
• ectromelia
• monkeypox
• rabbitpox
• smallpox
• vaccinia

Financial & competing interests disclosure

This work was supported in part by Contract HHSN272201000039I/HHSN27200007/A43 from the Virology Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported in part by Contract HHSN272201000039I/HHSN27200007/A43 from the Virology Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.