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

ABSTRACT ST-246, a potent orthopoxvirus egress inhibitor, is safe and effective at preventing disease and death in studies of small-animal models involving challenge by several different pathogenic poxviruses. In this report, the antiviral efficacy of ST-246 in treatment of nonhuman primates infected with variola virus or monkeypox virus was assessed. The data indicate that oral dosing once per day with ST-246 protects animals from poxvirus disease, as measured by reductions in viral load and numbers of lesions and enhancement of survival.

[1]  G. Gronvall.  Medical Aspects of Biological Warfare Edited by Zygmunt F. Dembek Falls Church, Virginia: Office of The Surgeon General, United States Army; Washington, DC: Borden Institute, Walter Reed Army Medical Center, 2007. 694 pp., Illustrated. $72.25 (hardcover) , 2009 .

[2]  R. Jordan,et al.  Evaluation of orally delivered ST-246 as postexposure prophylactic and antiviral therapeutic in an aerosolized rabbitpox rabbit model. , 2008, Antiviral research.

[3]  S. Weber,et al.  Severe eczema vaccinatum in a household contact of a smallpox vaccinee. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  Kevin F. Jones,et al.  Single-Dose Safety and Pharmacokinetics of ST-246, a Novel Orthopoxvirus Egress Inhibitor , 2008, Antimicrobial Agents and Chemotherapy.

[5]  Kevin F. Jones,et al.  Immune responses to the smallpox vaccine given in combination with ST-246, a small-molecule inhibitor of poxvirus dissemination , 2007, Vaccine.

[6]  R. Jordan,et al.  Synergistic Efficacy of the Combination of ST-246 with CMX001 against Orthopoxviruses , 2007, Antimicrobial Agents and Chemotherapy.

[7]  E. Marris.  Dramatic rescue relieves rare case of smallpox infection , 2007, Nature Medicine.

[8]  M. Siirin,et al.  Efficacy of the antipoxvirus compound ST-246 for treatment of severe orthopoxvirus infection. , 2007, The American journal of tropical medicine and hygiene.

[9]  R. Buller,et al.  Human monkeypox: an emerging zoonotic disease. , 2007, Future microbiology.

[10]  R. Jordan,et al.  Efficacy of Delayed Treatment with ST-246 Given Orally against Systemic Orthopoxvirus Infections in Mice , 2006, Antimicrobial Agents and Chemotherapy.

[11]  J. Sejvar,et al.  Clinical characteristics of human monkeypox, and risk factors for severe disease. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  R. Jordan,et al.  An Orally Bioavailable Antipoxvirus Compound (ST-246) Inhibits Extracellular Virus Formation and Protects Mice from Lethal Orthopoxvirus Challenge , 2005, Journal of Virology.

[13]  K. Kanefuji,et al.  Individual Reference Intervals of Hematological and Serum Biochemical Parameters in Cynomolgus Monkeys , 2005, International journal of toxicology.

[14]  I. Damon,et al.  Characterization of Acute-Phase Humoral Immunity to Monkeypox: Use of Immunoglobulin M Enzyme-Linked Immunosorbent Assay for Detection of Monkeypox Infection during the 2003 North American Outbreak , 2005, Clinical Diagnostic Laboratory Immunology.

[15]  D. Relman,et al.  Exploring the potential of variola virus infection of cynomolgus macaques as a model for human smallpox. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  P. Earl,et al.  Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox , 2004, Nature.

[17]  Eric Gross.  Update: multistate outbreak of monkeypox--Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. , 2003, MMWR. Morbidity and mortality weekly report.

[18]  R. Whitley,et al.  Smallpox: a potential agent of bioterrorism. , 2003, Antiviral research.

[19]  Update: multistate outbreak of monkeypox--Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. , 2003, MMWR. Morbidity and mortality weekly report.

[20]  M. Law,et al.  The formation and function of extracellular enveloped vaccinia virus. , 2002, The Journal of general virology.

[21]  P. Formenty,et al.  Outbreaks of Disease Suspected of Being Due to Human Monkeypox Virus Infection in the Democratic Republic of Congo in 2001 , 2002, Journal of Clinical Microbiology.

[22]  Philip K. Russell,et al.  Botulinum toxin as a biological weapon: medical and public health management. , 2001, JAMA.

[23]  R. Pebody,et al.  Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997. , 2001, Emerging infectious diseases.

[24]  Philip K. Russell,et al.  Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. , 1999, JAMA.

[25]  Philip K. Russell,et al.  Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. , 1999, JAMA.