Anti-SARS drug screening by molecular docking

• Published in: Amino acids Vol. 31; no. 1; pp. 73 - 80
• Main Authors: Wei, D-Q, Zhang, R, Du, Q-S, Gao, W-N, Li, Y, Gao, H, Wang, S-Q, Zhang, X, Li, A-X, Sirois, S, Chou, K-C
• Format: Journal Article
• Language: English
• Published: Austria Springer Nature B.V 01-07-2006; Springer-Verlag
• Subjects: Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Binding Sites; Drug Design; Hydrogen Bonding; Ligands; Microbial Sensitivity Tests; Models, Molecular; Protein Conformation; SARS coronavirus; Severe acute respiratory syndrome-related coronavirus - drug effects; Structure-Activity Relationship
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-006-0361-7

Starting from a collection of 1386 druggable compounds obtained from the 3D pharmacophore search, we performed a similarity search to narrow down the scope of docking studies. The template molecule is KZ7088 (Chou et al., 2003, Biochem Biophys Res Commun 308: 148-151). The MDL MACCS keys were used to fingerprint the molecules. The Tanimoto coefficient is taken as the metric to compare fingerprints. If the similarity threshold was 0.8, a set of 50 unique hits and 103 conformers were retrieved as a result of similarity search. The AutoDock 3.011 was used to carry out molecular docking of 50 ligands to their macromolecular protein receptors. Three compounds, i.e., C(28)H(34)O(4)N(7)Cl, C(21)H(36)O(5)N(6), and C(21)H(36)O(5)N(6), were found that may be promising candidates for further investigation. The main feature shared by these three potential inhibitors as well as the information of the involved side chains of SARS Cov Mpro may provide useful insights for the development of potent inhibitors against SARS enzyme.