Cited by 84Poxvirus research and outbreaksHerpesvirus Infections and TreatmentsVirology and Viral Diseases

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Progress in the Discovery of Compounds Inhibiting Orthopoxviruses in Animal Models

Smee, Donald F·2008·Antiviral Chemistry and Chemotherapy

DOI 10.1177/095632020801900302

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Abstract

Surrogate animal models must be used for testing antiviral agents against variola (smallpox) virus infections. Once developed, these compounds can be stockpiled for use in the event of a bioterrorist incident involving either variola or monkeypox virus, or used to treat an occasional serious orthopoxvirus infection, such as disseminated vaccinia complication following expo-sure to the live virus vaccine. Recently, considerable progress has been made in the discovery of novel anti-viral agents found active against orthopoxviruses in vivo. This includes the development of new animal models or refinement of existing ones for compound efficacy testing. Current mouse models employ ectromelia, cowpox and vaccinia (WR and IHD strains) viruses with respiratory (lung) or tail lesion infections commonly studied. Rabbitpox and vaccinia (WR strain) viruses are available for rabbit infections. Monkeypox and variola viruses are used for infecting monkeys. This review describes these and other animal models, and covers compounds found active in vivo from 2003 to date. Cidofovir, known to be active against orthopox virus infections prior to 2003, has been studied extensively over recent years. New compounds showing promise are orally active inhibitors of orthopoxvirus infections that include ether lipid prodrugs of cidofovir and ( S)-HPMPA, ST-246, N-meth-anocarbathymidine ( N-MCT) and SRI 21950 (a 4'-thio derivative of iododeoxyuridine). Another compound with high activity but requiring parenteral administration is HPMPO-DAPy. Further development of these compounds is warranted.

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Authors: Smee, D. F.
Affiliations: Utah State University (US)
Corresponding author: Smee, Donald F
ORCID: Smee, Donald F
Venue: Antiviral Chemistry and Chemotherapy
Publisher: SAGE Publications
Published: 2008-06
Volume: 19
Issue: 3
Pages: 115-124
ISSN: 0956-3202 (ISSN-L)
2040-2066
DOI: 10.1177/095632020801900302
OpenAlex: W2326918441
Cited by: 84
References: 77
Citations by year: 2026: 4 · 2025: 3 · 2024: 9 · 2023: 14 · 2022: 16 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 1
FWCI: 0.67
Type: journal article
Language: en
Open access: closed
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Antiviral chemistry & chemotherapy (publishedVersion)
PubMed (publishedVersion)
Funders: Utah State University
National Institutes of Health (n01ai15435-19-0-2)
National Institute of Allergy and Infectious Diseases (N01-AI-15435)
Topics: Life Sciences › Immunology and Microbiology › Virology › Poxvirus research and outbreaks
Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords: orthopoxvirus, antiviral agents, animal models, variola virus, monkeypox virus, vaccinia virus, ectromelia virus, cowpox virus, rabbitpox virus, cidofovir, ST-246, bioterrorism preparedness, smallpox
MeSH terms: Cidofovir, Adenine, Animals, Antiviral Agents, Benzamides, Cytosine, Disease Models, Animal, Humans, Phthalimides, Prodrugs, Orthopoxvirus, Isoindoles, Drug Discovery, Organophosphonates

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Progress in the Discovery of Compounds Inhibiting Orthopoxviruses in Animal Models

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