Discovery of Anti-SARS Coronavirus Drug Based on Molecular Docking and Database Screening

• 作 者: 陈海峰 姚建华 孙晶 李强 李丰 范波涛 袁身刚
• 机 构: Laboratory of Computer Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Scienc
• 出 处: Chinese Journal of Chemistry
• 发表日期: 2004年08期
• 关键词: Screening screening residue coronavirus porcine Figure screened putative aligned

The active site of 3CL proteinase (3CLpro) for coronavirus was identified by comparing the crystal structures of human and porcine coronavirus. The inhibitor of the main protein of rhinovirus (Ag7088) could bind with 3CLpro of human coronavirus, then it was selected as the reference for molecular docking and database screening. The ligands from two databases were used to search potential lead structures with molecular docking. Several structures from natural products and ACD-SC databases were found to have lower binding free energy with 3CLpro than that of Ag7088. These structures have similar hydrophobicity to Ag7088. They have complementary electrostatic potential and hydrogen bond acceptor and donor with 3CLpro, showing that the strategy of anti-SARS drug design based on molecular docking and database screening is feasible.

The active site of 3CL proteinase (3CLpro) for coronavirus was identified by comparing the crystal structures of human and porcine coronavirus. The inhibitor of the main protein of rhinovirus (Ag7088) could bind with 3CLpro of human coronavirus, then it was selected as the reference Several structures from natural products and ACD-SC databases were found to have lower binding free energy with 3CLpro than that of Ag7088. These structures from two databases were used to search potential lead structures with molecular docking. They have the complementary electrostatic potential and hydrogen bond acceptor and donor with 3CLpro, showing that the strategy of anti-SARS drug design based on molecular docking and database screening is feasible.