Viral serpin therapeutics: From concept to clinic

Hao Chen, Donghang Zheng, Jennifer Davids, Mee Yong Bartee, Erbin Dai, Liying Liu, Lyubomir Petrov, Colin Macaulay, Robert Thoburn, Eric Sobel, Richard Moyer, Grant McFadden, Alexandra Lucas

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Over the past 19 years, we have developed a novel myxoma virus-derived anti-inflammatory serine protease inhibitor, termed a serpin, as a new class of immunomodulatory therapeutic. This review will describe the initial identification of viral serpins with anti-inflammatory potential, beginning with preclinical analysis of viral pathogenesis and proceeding to cell and molecular target analyses, and successful clinical trial. The central aim of this review is to describe the development of two serpins, Serp-1 and Serp-2, as a new class of immune modulating drug, from inception to implementation. We begin with an overview of the approaches used for successful mining of the virus for potential serpin immunomodulators in viruses. We then provide a methodological overview of one inflammatory animal model used to test for serpin anti-inflammatory activity followed by methods used to identify cells in the inflammatory response system targeted by these serpins and molecular responses to serpin treatment. Finally, we provide an overview of our findings from a recent, successful clinical trial of the secreted myxomaviral serpin, Serp-1, in patients with unstable inflammatory coronary arterial disease.

Original languageEnglish (US)
Pages (from-to)301-329
Number of pages29
JournalMethods in Enzymology
StatePublished - Jun 24 2011
Externally publishedYes


  • Adhesion assay
  • Clinical trial
  • Flow cytometry
  • Immunotherapeutics
  • Mouse angioplasty model
  • PCR arrays
  • SERP-1
  • SERP-2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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