Tecovirimat

Tecovirimat

Identifiers
IUPAC name N-{3,5-Dioxo-4- azatetracyclo[5.3.2.0{2,6}.0{8,10}]dodec-11-en-4- yl}-4-(trifluoromethyl)benzamide
Synonyms	ST-246
UNII	F925RR824R Y
ChEMBL	CHEMBL1242629 Y
Chemical and physical data
Formula	C19H15F3N2O3
Molar mass	base: 376.3 g/mol
3D model (Jmol)	Interactive image
SMILES FC(F)(F)c1ccc(cc1)C(=O)NN1C(=O)C2C(C3C=CC2C2CC32)C1=O
InChI InChI=1S/C19H15F3N2O3/c20-19(21,22)9-3-1-8(2-4-9)16(25)23-24-17(26)14-10-5-6-11(13-7-12(10)13)15(14)18(24)27/h1-6,10-15H,7H2,(H,23,25) Y Key:CSKDFZIMJXRJGH-UHFFFAOYSA-N Y

Tecovirimat (ST-246) is an antiviral with activity against orthopoxviruses such as smallpox and is currently undergoing clinical trials. It was previously owned by Viropharma and discovered in collaboration with scientists at USAMRIID. It is currently owned and is synthesized by Siga Technologies, a drug development company in the biodefense arena. It works by blocking cellular transmission of the virus, thus preventing the disease. Tecovirimat has been effective in laboratory testing, with no serious side effects reported to date. Despite not yet having FDA approval for medical use, tecovirimat is stockpiled in the US Strategic National Stockpile as a defense against a smallpox outbreak.^[1]

Clinical study

The results of clinical trials involving tecovirimat supports its use against smallpox and other related orthopoxviruses. It has shown potential for a variety of uses including prophylaxis, as a post-exposure therapeutic, as a therapeutic and an adjunct to vaccination.^[2]

Tecovirimat can be taken orally and has recently been granted permission to conduct Phase II trials by the U.S. Food and Drug Administration (FDA). In phase I trials tecovirimat was generally well tolerated with no serious adverse events.^[3] Due to its importance for biodefense, the FDA has designated tecovirimat for 'fast-track' status, creating a path for expedited FDA review and eventual regulatory approval.

Operating mechanism

Tecovirimat is an orthopoxvirus egress inhibitor. Tecovirimat appears to target the V061 gene in cowpox, which is homologous to the vaccinia virus F13L. By targeting this gene, tecovirimat inhibits the function of a major envelope protein required for the production of extracellar virus. Thus the virus is prevented from leaving the cell, and the spread of the virus within the body is prevented.^[4]

References

1. ↑ Damon, Inger K.; Damaso, Clarissa R.; McFadden, Grant (2014). "Are We There Yet? The Smallpox Research Agenda Using Variola Virus". PLoS Pathogens. 10 (5): e1004108. doi:10.1371/journal.ppat.1004108. PMC 4006926. PMID 24789223. 
2. ↑ Siga Technologies
3. ↑ Jordan, R; Tien, D; Bolken, T. C.; Jones, K. F.; Tyavanagimatt, S. R.; Strasser, J; Frimm, A; Corrado, M. L.; Strome, P. G.; Hruby, D. E. (2008). "Single-Dose Safety and Pharmacokinetics of ST-246, a Novel Orthopoxvirus Egress Inhibitor". Antimicrobial Agents and Chemotherapy. 52 (5): 1721–1727. doi:10.1128/AAC.01303-07. PMC 2346641. PMID 18316519. 
4. ↑ Yang, G; Pevear, D. C.; Davies, M. H.; Collett, M. S.; Bailey, T; Rippen, S; Barone, L; Burns, C; Rhodes, G; Tohan, S; Huggins, J. W.; Baker, R. O.; Buller, R. L.; Touchette, E; Waller, K; Schriewer, J; Neyts, J; Declercq, E; Jones, K; Hruby, D; Jordan, R (2005). "An Orally Bioavailable Antipoxvirus Compound (ST-246) Inhibits Extracellular Virus Formation and Protects Mice from Lethal Orthopoxvirus Challenge". Journal of Virology. 79 (20): 13139–13149. doi:10.1128/JVI.79.20.13139-13149.2005. PMC 1235851. PMID 16189015.