Small molecules targeting severe acute respiratory syndrome human coronavirus.
Identifieur interne : 005063 ( Main/Exploration ); précédent : 005062; suivant : 005064Small molecules targeting severe acute respiratory syndrome human coronavirus.
Auteurs : Chung-Yi Wu [Taïwan] ; 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 WongSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2004.
Descripteurs français
- KwdFr :
- MESH :
- antagonistes et inhibiteurs : Protéines virales.
- pharmacologie : Antiviraux.
- Animaux, Cellules Vero, Cysteine endopeptidases, Cytométrie en flux, Endopeptidases, Réplication virale, Technique d'immunofluorescence, Technique de Western, Test ELISA, Virus du SRAS.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (pharmacology), Blotting, Western, Chlorocebus aethiops, Cysteine Endopeptidases, Endopeptidases, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluorescent Antibody Technique, SARS Virus (drug effects), Vero Cells, Viral Proteins (antagonists & inhibitors), Virus Replication (drug effects).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , pharmacology : Antiviral Agents.
- drug effects : SARS Virus, Virus Replication.
- Animals, Blotting, Western, Chlorocebus aethiops, Cysteine Endopeptidases, Endopeptidases, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluorescent Antibody Technique, Vero Cells.
Abstract
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, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).
DOI: 10.1073/pnas.0403596101
PubMed: 15226499
Affiliations:
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Cheng</name></author><author><name sortKey="Hsu, Hsien Hua" sort="Hsu, Hsien Hua" uniqKey="Hsu H" first="Hsien-Hua" last="Hsu">Hsien-Hua Hsu</name></author><author><name sortKey="Huang, Hsuan Cheng" sort="Huang, Hsuan Cheng" uniqKey="Huang H" first="Hsuan-Cheng" last="Huang">Hsuan-Cheng Huang</name></author><author><name sortKey="Wu, Douglass" sort="Wu, Douglass" uniqKey="Wu D" first="Douglass" last="Wu">Douglass Wu</name></author><author><name sortKey="Brik, Ashraf" sort="Brik, Ashraf" uniqKey="Brik A" first="Ashraf" last="Brik">Ashraf Brik</name></author><author><name sortKey="Liang, Fu Sen" sort="Liang, Fu Sen" uniqKey="Liang F" first="Fu-Sen" last="Liang">Fu-Sen Liang</name></author><author><name sortKey="Liu, Rai Shung" sort="Liu, Rai Shung" uniqKey="Liu R" first="Rai-Shung" last="Liu">Rai-Shung Liu</name></author><author><name sortKey="Fang, Jim Min" sort="Fang, Jim Min" uniqKey="Fang J" first="Jim-Min" last="Fang">Jim-Min Fang</name></author><author><name sortKey="Chen, Shui Tein" sort="Chen, Shui Tein" uniqKey="Chen S" first="Shui-Tein" last="Chen">Shui-Tein Chen</name></author><author><name sortKey="Liang, Po Huang" sort="Liang, Po Huang" uniqKey="Liang P" first="Po-Huang" last="Liang">Po-Huang Liang</name></author><author><name sortKey="Wong, Chi Huey" sort="Wong, Chi Huey" uniqKey="Wong C" first="Chi-Huey" last="Wong">Chi-Huey Wong</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (pharmacology)</term><term>Blotting, Western</term><term>Chlorocebus aethiops</term><term>Cysteine Endopeptidases</term><term>Endopeptidases</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Flow Cytometry</term><term>Fluorescent Antibody Technique</term><term>SARS Virus (drug effects)</term><term>Vero Cells</term><term>Viral Proteins (antagonists & inhibitors)</term><term>Virus Replication (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux (pharmacologie)</term><term>Cellules Vero</term><term>Cysteine endopeptidases</term><term>Cytométrie en flux</term><term>Endopeptidases</term><term>Protéines virales (antagonistes et inhibiteurs)</term><term>Réplication virale ()</term><term>Technique d'immunofluorescence</term><term>Technique de Western</term><term>Test ELISA</term><term>Virus du SRAS ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term><term>Virus Replication</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Chlorocebus aethiops</term><term>Cysteine Endopeptidases</term><term>Endopeptidases</term><term>Enzyme-Linked Immunosorbent Assay</term><term>Flow Cytometry</term><term>Fluorescent Antibody Technique</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules Vero</term><term>Cysteine endopeptidases</term><term>Cytométrie en flux</term><term>Endopeptidases</term><term>Réplication virale</term><term>Technique d'immunofluorescence</term><term>Technique de Western</term><term>Test ELISA</term><term>Virus du SRAS</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).</div></front></TEI><affiliations><list><country><li>Taïwan</li></country></list><tree><noCountry><name sortKey="Brik, Ashraf" sort="Brik, Ashraf" uniqKey="Brik A" first="Ashraf" last="Brik">Ashraf Brik</name><name sortKey="Chen, Shui Tein" sort="Chen, Shui Tein" uniqKey="Chen S" first="Shui-Tein" last="Chen">Shui-Tein Chen</name><name sortKey="Cheng, Yih Shyun E" sort="Cheng, Yih Shyun E" uniqKey="Cheng Y" first="Yih-Shyun E" last="Cheng">Yih-Shyun E. Cheng</name><name sortKey="Fang, Jim Min" sort="Fang, Jim Min" uniqKey="Fang J" first="Jim-Min" last="Fang">Jim-Min Fang</name><name sortKey="Hsu, Hsien Hua" sort="Hsu, Hsien Hua" uniqKey="Hsu H" first="Hsien-Hua" last="Hsu">Hsien-Hua Hsu</name><name sortKey="Huang, Hsuan Cheng" sort="Huang, Hsuan Cheng" uniqKey="Huang H" first="Hsuan-Cheng" last="Huang">Hsuan-Cheng Huang</name><name sortKey="Jan, Jia Tsrong" sort="Jan, Jia Tsrong" uniqKey="Jan J" first="Jia-Tsrong" last="Jan">Jia-Tsrong Jan</name><name sortKey="Juan, Hsueh Fen" sort="Juan, Hsueh Fen" uniqKey="Juan H" first="Hsueh-Fen" last="Juan">Hsueh-Fen Juan</name><name sortKey="Kuo, Chih Jung" sort="Kuo, Chih Jung" uniqKey="Kuo C" first="Chih-Jung" last="Kuo">Chih-Jung Kuo</name><name sortKey="Liang, Fu Sen" sort="Liang, Fu Sen" uniqKey="Liang F" first="Fu-Sen" last="Liang">Fu-Sen Liang</name><name sortKey="Liang, Po Huang" sort="Liang, Po Huang" uniqKey="Liang P" first="Po-Huang" last="Liang">Po-Huang Liang</name><name sortKey="Liu, Rai Shung" sort="Liu, Rai Shung" uniqKey="Liu R" first="Rai-Shung" last="Liu">Rai-Shung Liu</name><name sortKey="Ma, Shiou Hwa" sort="Ma, Shiou Hwa" uniqKey="Ma S" first="Shiou-Hwa" last="Ma">Shiou-Hwa Ma</name><name sortKey="Wong, Chi Huey" sort="Wong, Chi Huey" uniqKey="Wong C" first="Chi-Huey" last="Wong">Chi-Huey Wong</name><name sortKey="Wu, Douglass" sort="Wu, Douglass" uniqKey="Wu D" first="Douglass" last="Wu">Douglass Wu</name></noCountry><country name="Taïwan"><noRegion><name sortKey="Wu, Chung Yi" sort="Wu, Chung Yi" uniqKey="Wu C" first="Chung-Yi" last="Wu">Chung-Yi Wu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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