Display options
Cite
Grosenbach DW, Jordan R, Hruby DE. Development of the small-molecule antiviral ST-246 as a smallpox therapeutic. Future Virol. 2011;6(5):653-671doi: 10.2217/fvl.11.27.
Grosenbach, D. W., Jordan, R., & Hruby, D. E. (2011). Development of the small-molecule antiviral ST-246 as a smallpox therapeutic. Future virology, 6(5), 653-671. https://doi.org/10.2217/fvl.11.27
Grosenbach, Douglas W, et al. "Development of the small-molecule antiviral ST-246 as a smallpox therapeutic." Future virology vol. 6,5 (2011): 653-671. doi: https://doi.org/10.2217/fvl.11.27
Grosenbach DW, Jordan R, Hruby DE. Development of the small-molecule antiviral ST-246 as a smallpox therapeutic. Future Virol. 2011 May;6(5):653-671. doi: 10.2217/fvl.11.27. PMID: 21837250; PMCID: PMC3151656.
Copy Download .nbib Format: NLM
Share it on

Future Virol. 2011 May;6(5):653-671. doi: 10.2217/fvl.11.27.

Development of the small-molecule antiviral ST-246 as a smallpox therapeutic.

Future virology

Douglas W Grosenbach, Robert Jordan, Dennis E Hruby

Affiliations

  1. SIGA Technologies, Inc., 4575 SW Research Way, Suite 230, Corvallis, OR 97333, USA.

PMID: 21837250 PMCID: PMC3151656 DOI: 10.2217/fvl.11.27

Abstract

Naturally occurring smallpox has been eradicated, yet it remains as one of the highest priority pathogens due to its potential as a biological weapon. The majority of the US population would be vulnerable in a smallpox outbreak. SIGA Technologies, Inc. has responded to the call of the US government to develop and supply to the Strategic National Stockpile a smallpox antiviral to be deployed in the event of a smallpox outbreak. ST-246(®) (tecovirimat) was initially identified via a high-throughput screen in 2002, and in the ensuing years, our drug-development activities have spanned in vitro analysis, preclinical safety, pharmacokinetics and efficacy testing (all according to the 'animal rule'). Additionally, SIGA has conducted Phase I and II clinical trials to evaluate the safety, tolerability and pharmacokinetics of ST-246, bringing us to our current late stage of clinical development. This article reviews the need for a smallpox therapeutic and our experience in developing ST-246, and provides perspective on the role of a smallpox antiviral during a smallpox public health emergency.

References

  1. Curr Opin Infect Dis. 2008 Apr;21(2):153-6 - PubMed
  2. Nature. 2004 Mar 11;428(6979):182-5 - PubMed
  3. J Virol. 2005 Sep;79(18):11873-91 - PubMed
  4. Antivir Ther. 2007;12(8):1205-16 - PubMed
  5. Nat Med. 2003 Sep;9(9):1125-30 - PubMed
  6. J Clin Microbiol. 2007 Apr;45(4):1370-2 - PubMed
  7. J Gen Virol. 1980 Sep;50(1):89-100 - PubMed
  8. Am J Trop Med Hyg. 2007 Apr;76(4):768-73 - PubMed
  9. Vaccine. 2007 Apr 12;25(15):2787-99 - PubMed
  10. Curr Protoc Mol Biol. 2001 May;Chapter 16:Unit16.16 - PubMed
  11. Virology. 2007 Sep 15;366(1):73-83 - PubMed
  12. Antiviral Res. 2006 Mar;69(3):158-64 - PubMed
  13. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):838-43 - PubMed
  14. Vaccine. 2006 Mar 15;24(12):2065-70 - PubMed
  15. Viruses. 2010 Nov;2(11):2409-35 - PubMed
  16. Science. 1999 Feb 26;283(5406):1279-82 - PubMed
  17. Clin Infect Dis. 2008 Mar 15;46 Suppl 3:S157-67 - PubMed
  18. Antimicrob Agents Chemother. 2007 Nov;51(11):4118-24 - PubMed
  19. Vaccine. 2008 Feb 13;26(7):933-46 - PubMed
  20. Antimicrob Agents Chemother. 2009 Jun;53(6):2620-5 - PubMed
  21. MMWR Morb Mortal Wkly Rep. 2009 May 22;58(19):532-6 - PubMed
  22. Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16262-7 - PubMed
  23. Emerg Infect Dis. 2004 May;10(5):832-41 - PubMed
  24. Clin Infect Dis. 2003 Jul 15;37(2):251-71 - PubMed
  25. Clin Infect Dis. 2008 May 15;46(10):1555-61 - PubMed
  26. Virology. 2005 Oct 10;341(1):91-101 - PubMed
  27. Antimicrob Agents Chemother. 2005 Jul;49(7):2634-41 - PubMed
  28. Antimicrob Agents Chemother. 2009 May;53(5):1817-22 - PubMed
  29. J Virol. 1993 Aug;67(8):4732-41 - PubMed
  30. Future Microbiol. 2007 Feb;2(1):17-34 - PubMed
  31. Emerg Infect Dis. 2001 May-Jun;7(3):434-8 - PubMed
  32. Science. 2003 May 9;300(5621):880-1 - PubMed
  33. Antimicrob Agents Chemother. 2007 Feb;51(2):689-95 - PubMed
  34. J Virol. 1991 Nov;65(11):5910-20 - PubMed
  35. J Virol. 1996 Jan;70(1):272-81 - PubMed
  36. Epidemiology. 2004 May;15(3):264-70 - PubMed
  37. Emerg Infect Dis. 2001 Nov-Dec;7(6):959-69 - PubMed
  38. Nat Med. 2005 Jul;11(7):740-7 - PubMed
  39. Virol J. 2009 Apr 28;6:44 - PubMed
  40. Antiviral Res. 2008 Aug;79(2):121-7 - PubMed
  41. Eff Clin Pract. 2002 Mar-Apr;5(2):84-90 - PubMed
  42. Vaccine. 2008 Jan 24;26(4):581-8 - PubMed
  43. Clin Infect Dis. 2004 Dec 1;39(11):1668-73 - PubMed
  44. Antimicrob Agents Chemother. 2009 Dec;53(12):4999-5009 - PubMed
  45. Vaccine. 2006 Apr 24;24(17):3686-94 - PubMed
  46. Cytokine. 1992 Jul;4(4):281-6 - PubMed
  47. J Virol. 2005 Oct;79(20):13139-49 - PubMed
  48. Virology. 1994 Jun;201(2):215-40 - PubMed
  49. Curr Protoc Mol Biol. 2001 May;Chapter 16:Unit16.17 - PubMed
  50. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4152-7 - PubMed
  51. Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15196-200 - PubMed
  52. J Virol. 2005 Jun;79(12):7845-51 - PubMed
  53. PLoS Med. 2006 Aug;3(8):e272 - PubMed
  54. Epidemiol Infect. 2004 Jan;132(1):19-25 - PubMed
  55. J Virol. 2004 May;78(9):4433-43 - PubMed
  56. JAMA. 1997 Aug 6;278(5):399-411 - PubMed
  57. JAMA. 1999 Jun 9;281(22):2127-37 - PubMed
  58. J Infect Dis. 1970 Oct;122(4):303-9 - PubMed
  59. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10935-40 - PubMed
  60. Arch Pediatr Adolesc Med. 2005 Nov;159(11):1022-5 - PubMed
  61. Int J Infect Dis. 2004 Oct;8 Suppl 2:S31-44 - PubMed
  62. Vaccine. 2005 May 9;23(25):3301-9 - PubMed
  63. Antimicrob Agents Chemother. 2008 May;52(5):1721-7 - PubMed
  64. J Immunol. 2006 Aug 15;177(4):2552-64 - PubMed
  65. Lab Invest. 2001 Dec;81(12):1581-600 - PubMed
  66. Nature. 2006 Feb 9;439(7077):745-8 - PubMed
  67. Vaccine. 2010 Dec 16;29(2):289-303 - PubMed
  68. J Gen Virol. 2002 Dec;83(Pt 12):2915-2931 - PubMed
  69. Clin Infect Dis. 2004 Jun 15;38(12):1749-53 - PubMed
  70. J Virol. 2006 Jun;80(11):5179-88 - PubMed
  71. Euro Surveill. 2004 Dec 15;9(12):E7-8 - PubMed
  72. Antimicrob Agents Chemother. 2005 Aug;49(8):3153-62 - PubMed

Publication Types

Grant support