title: Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection.
abstract: Since the eradication of naturally occurring smallpox in 1980, the fear that variola virus could be used as a biological weapon has become real. Over the last 10 years, emergency preparedness programs have been launched to protect populations against a smallpox outbreak or the possible emergence in humans of other orthopoxvirus infections, such as monkeypox. Vaccination against smallpox was responsible for its eradication, but was linked with high rates of adverse events and contraindications. In this context, intensive research in the poxvirus field has led to the development of safer vaccines and to an increase in the number of anti-poxvirus agents in the pipeline. SIGA Technologies Inc, under license from ViroPharma Inc, is developing tecovirimat (ST-246). Tecovirimat is a novel antiviral that inhibits the egress of orthopoxviruses by targeting viral p37 protein orthologs. The development of tecovirimat during the last 5 years for the treatment of smallpox and for its potential use as adjunct to smallpox vaccine is reviewed here.
authors.affiliation: Katholieke Universiteit Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Duraffour
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000600:supply & distribution / Q000627:therapeutic use*; D001549:Benzamides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000600:supply & distribution / Q000627:therapeutic use*; D001694:Biological Warfare; D002959:Civil Defense; D004353:Drug Evaluation, Preclinical; D006801:Humans; D054833:Isoindoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000600:supply & distribution / Q000627:therapeutic use*; D010330:Patents as Topic; D012899:Smallpox / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D012900:Smallpox Vaccine / Q000600:supply & distribution; D016896:Treatment Outcome; D012901:Variola virus / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors*; D010797:Phthalimides
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D054833:Isoindoles; D012900:Smallpox Vaccine; D014759:Viral Envelope Proteins; C505045:tecovirimat; D010797:Phthalimides