Anti-SARS drug screening by molecular docking

Abstract

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.

Isolation and Characterization of a Trypsin-Chymotrypsin Inhibitor from the Seeds of Green Lentil (Lens culinaris)

“…Protease inhibitors and their selectivity have formed a topic of intense investigations [such as inhibitors of caspases (cysteinyl aspartate-specific proteases) for finding drugs to treat neurodegenerative diseases, ischemic injury and cancer [1][2][3]; BACE1, BACE2, and cathepsin-E inhibitor for treating Alzheimer Disease [4][5][6][7]; HIV-1 protease inhibitor for treating AIDS [8][9][10][11][12]; coronavirus main protease inhibitor for treating SARS [13][14][15][16][17][18][19] [17,18,[20][21][22][23]. Plants produce several types of protease inhibitors including Bowman-Birk inhibitors Kunitz inhibitors and squash inhibitors [24][25][26][27][28].…”

Discovery of Anti-Hiv Drugs Using Computer Aided Drug Designing Tools

“…Actually, the molecule thus modified can be compared to a "distorted key" which can be inserted into a lock but can neither open the lock nor be pulled out from it, spontaneously becoming an ideal competitive inhibitor against the SARS proteinase. Then we did a docking study of their proposed AVLQSGFR octapeptide to the SARS-CoV Mpro based on the three-dimensional structure of SARS coronavirus main proteinase through a homologous approach [9][10][11][12][13]. The binding results show that the octapeptide is bound to the SARS proteinase through six hydrogen bonds.…”

Interactions of CYP2C9 with Different Substrates and its Implications for Metabolic Mechanism

“…The similar methods have been used to investigate the binding interaction of alpha 7 nAChR dimmer with GTS-21 [11], CYP2C19 [12], Xylose reductases [13], and for anti-SARS drug screening [14]. For comparison, flurbiprofen has been docked to the crystal structure with PDB code 1R9O, and then optimized by MD simulations.…”