Nonhuman Primates Are Protected from Smallpox Virus or Monkeypox Virus Challenges by the Antiviral Drug ST-246

Huggins, John W.; Goff, Arthur J.; Hensley, Lisa E.; Mucker, Eric M.; Shamblin, Josh; Wlazlowski, Carly; Johnson, Wendy M.; Chapman, Jennifer L.; Larsen, Tom; Twenhafel, Nancy; Karem, Kevin L.; Damon, Inger K.; Byrd, Chelsea M.; Bolken, Tove’ C.; Jordan, Robert; Hruby, Dennis E.

doi:10.1128/aac.00021-09

Cited by 154 publications

(158 citation statements)

References 23 publications

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“…47 After IV challenge with 5 Â 10 7 pfu of MPXV, cynomolgus macaques develop a generalized vesiculopustular rash that begins on the head and extremities and then spreads to the rest of the body, much like human MPXV and VARV. 48 Clinically, there is fever with leukocytosis, and at necropsy there is prominent lymphadenopathy with splenomegaly and pulmonary edema. 48 This animal model has been used for efficacy studies of an antiviral therapeutic agent.…”

Section: 106mentioning

confidence: 99%

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Animal Models of Orthopoxvirus Infection

et al. 2010

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Smallpox was one of the most devastating diseases known to humanity. Although smallpox was eradicated through a historically successful vaccination campaign, there is concern in the global community that either Variola virus (VARV), the causative agent of smallpox, or another species of Orthopoxvirus could be used as agents of bioterrorism. Therefore, development of countermeasures to Orthopoxvirus infection is a crucial focus in biodefense research, and these efforts rely on the use of various animal models. Smallpox typically presented as a generalized pustular rash with 30 to 40% mortality, and although smallpox-like syndromes can be induced in cynomolgus macaques with VARV, research with this virus is highly restricted; therefore, animal models with other orthopoxviruses have been investigated. Monkeypox virus causes a generalized vesiculopustular rash in rhesus and cynomolgus macaques and induces fatal systemic disease in several rodent species. Ectromelia virus has been extensively studied in mice as a model of orthopoxviral infection in its natural host. Intranasal inoculation of mice with some strains of vaccinia virus produces fatal bronchopneumonia, as does aerosol or intranasal inoculation of mice with cowpox virus. Rabbitpox virus causes pneumonia and fatal systemic infections in rabbits and can be naturally transmitted between rabbits by an aerosol route similar to that of VARV in humans. No single animal model recapitulates all known aspects of human Orthopoxvirus infections, and each model has its advantages and disadvantages. This article provides a brief review of the Orthopoxvirus diseases of humans and the key pathologic features of animal models of Orthopoxvirus infections.

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Section: 106mentioning

confidence: 99%

“…In a subsequent study performed to assess the efficacy of an antiviral drug, VARV was administered to cynomolgus macaques (IV, 1 Â 10 8 pfu), and the disease endpoints observed in control animals (lesions and death) were similar to those seen in humans. 48 …”

Section: Animal Models Of Varv Infectionmentioning

confidence: 99%

Animal Models of Orthopoxvirus Infection

et al. 2010

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“…The antiviral ampleness of ST-246 in treatment of nonhuman primates infected with variola disease or monkeypox was reviewed. The information show that oral dosing once every day with ST-246 shields animals from poxvirus disease, as measured by decreases in viral load and quantities of lesions and improvement of survival (Huggins et al, 2009). …”

Section: Need For Having An Antiviral Drug St-246mentioning

confidence: 99%

Monkeypox Transmission, Need and Treatment of Humans with an Antiviral Drug

Jabeen

Umbreen

2017

Int J Soc Sci Mgt

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Monkeypox is a viral zoonotic disease belongs to the family Poxviridae and Orthopoxvirus genus. Transmission of monkey pox is through direct contact with infected animal and blood. Human to human transmission occur through respiratory route but previously so many studies are conducted to prove that monkey pox viruse was not transmitted through the respiratory route both in animals and humans. But now monkey pox is able to survive in humans due to genetic changes and human to human transmission is possible. Because it can be used as bioweapon, So there is a great need of having an antiviral drug which is effective against monkey pox virus.ST 246 proved effective in vivo and in vitro in infected animals and trials done safely on non-infected humans but no data is available about the effectiveness of ST 246 on monkey pox or Orthopox infected human treated with ST 246.

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“…Key events of a natural pox infection such as the alteration of the upper respiratory tract, a primary viremic phase and prodromal phases are skipped. Nevertheless, these models cause a systemic disease with mortality rates of up to 100 % and can be used to evaluate the efficacy of anti-OPXV therapeutics (Huggins et al, 2009) and vaccines (summarized in Schmitt et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…The experiments must be performed in a biosafety level (BSL)-3 containment facility. Furthermore, the VARV animal model, a suitable model for hemorrhagic smallpox used in some drug efficacy studies (Huggins et al, 2009;Mucker et al, 2013) as well as for pathogenesis studies (Wahl-Jensen et al, 2011), is restricted to two BSL-4 laboratories worldwide (Centers for Disease Control and Prevention, USA; and State Research Center of Virology and Biotechnology, Russia). Thus, alternative models are needed, and those based on CPXV, which is classified as a BSL-2 pathogen, are increasing in interest.…”

Section: Introductionmentioning

confidence: 99%

Limited susceptibility of rhesus macaques to a cowpox virus isolated from a lethal outbreak among New World monkeys

et al. 2017

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Abstract. This study was undertaken to investigate the susceptibility of rhesus monkeys to the calpox virus, an orthopoxvirus (OPXV) of the Cowpox virus species (CPXV), which is uniformly lethal in common marmosets. Six rhesus monkeys were either intravenously (i.v.) or intranasally (i.n.) exposed to the virus. Monitoring of the macaques after viral exposure included physical examinations, the determination of viral load by real-time PCR and plaque assay, and the analysis of humoral responses. Two i.v. inoculated animals developed numerous classical pox lesions that started after inoculation at days 7 and 10. Both animals became viremic and seroconverted. They exhibited maximal numbers of lesions of approximately 50 and 140 by day 21. One animal completely recovered, while the other one suffered from a phlegmonous inflammation of a leg initially induced by a secondarily infected pox lesion and was euthanized for animal welfare reasons. In contrast to previous pathogenicity studies with the calpox virus in marmosets, none of the four animals inoculated intranasally with doses of the calpox virus exceeding those used in marmosets by orders of magnitude showed typical clinical symptoms. No viral DNA was detectable in the blood of those animals, but three animals seroconverted. In two of these three animals, infectious virus was sporadically isolated from saliva. This indicates that rhesus monkeys are less susceptible to calpox virus infection, which limits their use in further intervention studies with OPXV.

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Nonhuman Primates Are Protected from Smallpox Virus or Monkeypox Virus Challenges by the Antiviral Drug ST-246

Cited by 154 publications

References 23 publications

Animal Models of Orthopoxvirus Infection

Animal Models of Orthopoxvirus Infection

Monkeypox Transmission, Need and Treatment of Humans with an Antiviral Drug

Limited susceptibility of rhesus macaques to a cowpox virus isolated from a lethal outbreak among New World monkeys

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