Binding mechanism of coronavirus main proteinase with ligands and its implication to drug design against SARS

作者：Chou KC^*; Wei DQ; Zhong WZ

来源：Biochemical and Biophysical Research Communications, 2003, 308(1): 148-151.

DOI：10.1016/S0006-291X(03)01342-1

• SARS
• coronavirus proteinase
• KZ7088
• AG7088
• binding pocket
• octapeptide substrate
• " distorted key" mechanism

In order to stimulate the development of drugs against severe acute respiratory syndrome (SARS), based on the atomic coordinates of the SARS coronavirus main proteinase determined recently [Science 13 (May) (2003) (online)], studies of docking KZ7088 (a derivative of AG7088) and the AVLQSGFR octapeptide to the enzyme were conducted. It has been observed that both the above compounds interact with the active site of the SARS enzyme through six hydrogen bonds. Also, a clear definition of the binding pocket for KZ7088 has been presented. These findings may provide a solid basis for subsite analysis and mutagenesis relative to rational design of highly selective inhibitors for therapeutic application. Meanwhile, the idea of how to develop inhibitors of the SARS enzyme based on the knowledge of its own peptide substrates (the so-called "distorted key" approach) was also briefly elucidated.

• 出版日期2003-8-15
• 单位天津师范大学