Viruses 2010, 2(11), 2409-2435; doi:10.3390/v2112409
Review

Development of ST-246® for Treatment of Poxvirus Infections

* email, email, email and email
Received: 18 September 2010; in revised form: 26 October 2010 / Accepted: 26 October 2010 / Published: 3 November 2010
(This article belongs to the Special Issue Antivirals Against Poxviruses)
Download PDF [422 KB, uploaded 3 November 2010]
Abstract: ST-246 (Tecovirimat) is a small synthetic antiviral compound being developed to treat pathogenic orthopoxvirus infections of humans. The compound was discovered as part of a high throughput screen designed to identify inhibitors of vaccinia virus-induced cytopathic effects. The antiviral activity is specific for orthopoxviruses and the compound does not inhibit the replication of other RNA- and DNA-containing viruses or inhibit cell proliferation at concentrations of compound that are antiviral. ST-246 targets vaccinia virus p37, a viral protein required for envelopment and secretion of extracellular forms of virus. The compound is orally bioavailable and protects multiple animal species from lethal orthopoxvirus challenge. Preclinical safety pharmacology studies in mice and non-human primates indicate that ST-246 is readily absorbed by the oral route and well tolerated with the no observable adverse effect level (NOAEL) in mice measured at 2000 mg/kg and the no observable effect level (NOEL) in non-human primates measured at 300 mg/kg. Drug substance and drug product processes have been developed and commercial scale batches have been produced using Good Manufacturing Processes (GMP). Human phase I clinical trials have shown that ST-246 is safe and well tolerated in healthy human volunteers. Based on the results of the clinical evaluation, once a day dosing should provide plasma drug exposure in the range predicted to be antiviral based on data from efficacy studies in animal models of orthopoxvirus disease. These data support the use of ST-246 as a therapeutic to treat pathogenic orthopoxvirus infections of humans.
Keywords: Smallpox; ST-246; Tecovirimat; orthopoxvirus; p37; egress inhibitor; antiviral drug
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Jordan, R.; Leeds, J.M.; Tyavanagimatt, S.; Hruby, D.E. Development of ST-246® for Treatment of Poxvirus Infections. Viruses 2010, 2, 2409-2435.

AMA Style

Jordan R, Leeds JM, Tyavanagimatt S, Hruby DE. Development of ST-246® for Treatment of Poxvirus Infections. Viruses. 2010; 2(11):2409-2435.

Chicago/Turabian Style

Jordan, Robert; Leeds, Janet M.; Tyavanagimatt, Shanthakumar; Hruby, Dennis E. 2010. "Development of ST-246® for Treatment of Poxvirus Infections." Viruses 2, no. 11: 2409-2435.


Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert