Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy |
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Authors: | S-Q Wang Q-S Du K Zhao A-X Li D-Q Wei K-C Chou |
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Institution: | (1) College of Pharmaceuticals and Biotechnology, Tianjin University, Tianjin, China;(2) Institute of Bioinformatics and Drug Discovery, Tianjin Normal University, Tianjin, China;(3) Tianjin Wujing Medical Institute, Tianjin, China;(4) College of Life Science and Technology, Shanghai Jiaotong University, Shanghai, China;(5) Gordon Life Science Institute, San Diego, CA, U.S.A. |
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Abstract: | Summary. Recently Simmons et al. reported a new mechanism for SARS virus entry into target cells, where MDL28170 was identified as
an efficient inhibitor of CTSL-meditated substrate cleavage with IC50 of 2.5 nmol/l. Based on the molecule fingerprint searching method, 11 natural molecules were found in the Traditional Chinese
Medicines Database (TCMD). Molecular simulation indicates that the MOL376 (a compound derived from a Chinese medicine herb
with the therapeutic efficacy on the human body such as relieving cough, removing the phlegm, and relieving asthma) has not
only the highest binding energy with the receptor but also the good match in geometric conformation. It was observed through
docking studies that the van der Waals interactions made substantial contributions to the affinity, and that the receptor
active pocket was too large for MDL21870 but more suitable for MOL736. Accordingly, MOL736 might possibly become a promising
lead compound for CTSL inhibition for SARS therapy. |
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Keywords: | : Severe acute respiratory syndrome (SARS) – MDL28170 – KZ7088 – Molecular simulation – Docking – Structural bioinformatics |
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