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. 2006 Sep 29;33(1):129–135. doi: 10.1007/s00726-006-0403-1

Virtual screening for finding natural inhibitor against cathepsin-L for SARS therapy

S-Q Wang 1, Q-S Du 2,5, K Zhao 1, A-X Li 3, D-Q Wei 4,5, K-C Chou 5
PMCID: PMC7087620  PMID: 16998715

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.

Keywords: Keywords: Severe acute respiratory syndrome (SARS) – MDL28170 – KZ7088 – Molecular simulation – Docking – Structural bioinformatics

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