Small molecules targeting severe acute respiratory syndrome human coronavirus

• DOI: 10.1073/pnas.0403596101
• Publication Date: 2004-06-29T00:15:08Z
• Authors: Chung-Yi Wu; Jia-Tsrong Jan; Shiou-Hwa Ma; Chih-Jung Kuo; Hsueh-Fen Juan; Yih-Shyun E. Cheng; Hsien-Hua Hsu; Hsuan-Cheng Huang; Douglass Wu; Ashraf Brik; Fu-Sen Liang; Rai-Shung Liu; Jim-Min Fang; Shui-Tein Chen; Po-Huang Liang; Chi-Huey Wong
• Keywords: Coronavirus; Betacoronavirus; 2019-20 coronavirus outbreak; Coronaviridae; Sars virus; Coronavirus Infections

Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, synthetic compounds identify anti-SARS agents. Of >10,000 tested, approximately 50 were found active at 10 microM; among these compounds, two are drugs (Reserpine 13 Aescin 5) several in clinical development. These tested again, 2-6, 10, showed 3 microM. The 50% inhibitory concentrations for the inhibition viral replication (EC(50)) host growth (CC(50)) then measured selectivity index (SI = CC(50)/EC(50)) determined. EC(50), based on ELISA, SI Reserpine, Aescim, Valinomycin 3.4 microM 7.3), 6.0 2.5), 0.85 80), respectively. Additional studies carried out further understand mode action some including Western blot analysis, immunofluorescence flow cytometry assays, 3CL protease entry. particular interest anti-HIV agents, one as entry blocker other inhibitor (K(i) 0.6 microM).