title: Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs.
abstract: The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors.
authors.affiliation: HKU-Pasteur Research Center, 8 Sassoon Road, Pokfulam, Hong Kong. xwzhang@hkucc.hku.hk
authors.forename: Xue Wu
authors.initials: XW
authors.lastname: Zhang
authors.forename: Yee Leng
authors.initials: YL
authors.lastname: Yap
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry; D000977:Antiparasitic Agents / Q000737:chemistry; D014150:Antipsychotic Agents / Q000737:chemistry; D000998:Antiviral Agents / Q000737:chemistry* / Q000627:therapeutic use; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D061466:Lopinavir; D015394:Molecular Structure; D009534:Niclosamide / Q000737:chemistry; D011395:Promazine / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D011744:Pyrimidinones / Q000737:chemistry; D019438:Ritonavir / Q000737:chemistry; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy*
chemical_list: D019380:Anti-HIV Agents; D000977:Antiparasitic Agents; D014150:Antipsychotic Agents; D000998:Antiviral Agents; D005663:Furans; D011480:Protease Inhibitors; D011743:Pyrimidines; D011744:Pyrimidinones; C493768:UC2 compound; D061466:Lopinavir; D009534:Niclosamide; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases; D019438:Ritonavir; D011395:Promazine