The Evaluation of Non-Viral Substrates of the HIV Protease as Leads in the Design of Inhibitors for Aids Therapy

  • Alfredo G. Tomasselli
  • John O. Hui
  • Tomi K. Sawyer
  • Suvit Thaisrivongs
  • Jackson B. Hester
  • Robert L. Heinrikson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 306)


The aspartyl protease encoded within the pol gene of human immunodeficiency virus (HIV) provides a target for therapeutic intervention in the treatment of acquired immunodeficiency syndrome (AIDS). This enzyme is indispensable for processing the viral gag and gag/pol polyproteins which takes place during the final maturation step of the viral life cycle. Blocking of protease action by inhibitors1–4 or by mutagenesis5 results in production of immature, non-infectious viral particles. Accordingly, the past few years have witnessed a world-wide effort to discover inhibitors of the HIV protease with antiviral activity. By and large, the design of such inhibitors has been based upon the specificity of the HIV protease for its natural polyprotein substrates. This data base of information is limited, and we have sought to expand it by evaluation of non-viral proteins as substrates of the enzyme.6–9 The present chapter describes how information thus derived can be applied to the design of protease inhibitors with potent antiviral activity.


Human Immunodeficiency Virus Simian Immunodeficiency Virus Renin Inhibitor Aspartyl Protease Potent Antiviral Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Alfredo G. Tomasselli
    • 1
  • John O. Hui
    • 1
  • Tomi K. Sawyer
    • 1
  • Suvit Thaisrivongs
    • 1
  • Jackson B. Hester
    • 1
  • Robert L. Heinrikson
    • 1
  1. 1.Upjohn LaboratoriesThe Upjohn CompanyKalamazooUSA

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