Wang S-Q, Du Q-S, Zhao K, Li A-X, Wei D-Q, Chou K-C
College of Pharmaceuticals and Biotechnology, Tianjin University, Tianjin, China.
Amino Acids. 2007 Jul;33(1):129-35. doi: 10.1007/s00726-006-0403-1. Epub 2006 Sep 29.
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 IC(50) 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.
最近，西蒙斯等人报道了严重急性呼吸综合征（SARS）病毒进入靶细胞的一种新机制，其中MDL28170被确定为组织蛋白酶L（CTSL）介导的底物切割的有效抑制剂，其半数抑制浓度（IC50）为2.5纳摩尔/升。基于分子指纹搜索方法，在中药数据库（TCMD）中发现了11种天然分子。分子模拟表明，MOL376（一种源自具有止咳、祛痰、平喘等人体治疗功效的中药材的化合物）不仅与受体具有最高的结合能，而且在几何构象上也匹配良好。通过对接研究观察到，范德华相互作用对亲和力有很大贡献，并且受体活性口袋对MDL21870来说太大，但对MOL736更合适。因此，MOL736可能成为一种有前途的用于抑制CTSL以治疗SARS的先导化合物。
