Indomethacin has a potent antiviral activity against SARS coronavirus
Identifieur interne : 000568 ( PascalFrancis/Curation ); précédent : 000567; suivant : 000569Indomethacin has a potent antiviral activity against SARS coronavirus
Auteurs : Carla Amici [Italie] ; Antonino Di Caro [Italie] ; Alessandra Ciucci [Italie] ; Lucia Chiappa [Italie] ; Concetta Castilletti [Italie] ; Vito Martella [Italie] ; Nicola Decaro [Italie] ; Canio Buonavoglia [Italie] ; Maria R. Capobianchi [Italie] ; M. Gabriella Santoro [Italie]Source :
- Antiviral therapy : (London) [ 1359-6535 ] ; 2006.
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- Pascal (Inist)
English descriptors
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Abstract
Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. Objectives: Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication. Methods: Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID50, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after 35S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO). Results: Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs. Conclusions: The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.
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Spallanzani'</s1><s2>Rome</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Martella, Vito" sort="Martella, Vito" uniqKey="Martella V" first="Vito" last="Martella">Vito Martella</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Faculty of Veterinary Medicine, University of Bari</s1><s2>Bari</s2><s3>ITA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Decaro, Nicola" sort="Decaro, Nicola" uniqKey="Decaro N" first="Nicola" last="Decaro">Nicola Decaro</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Faculty of Veterinary Medicine, University of Bari</s1><s2>Bari</s2><s3>ITA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Buonavoglia, Canio" sort="Buonavoglia, Canio" uniqKey="Buonavoglia C" first="Canio" last="Buonavoglia">Canio Buonavoglia</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Faculty of Veterinary Medicine, University of Bari</s1><s2>Bari</s2><s3>ITA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Capobianchi, Maria R" sort="Capobianchi, Maria R" uniqKey="Capobianchi M" first="Maria R." last="Capobianchi">Maria R. Capobianchi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Virology, National Institute for Infectious Diseases 'L. Spallanzani'</s1><s2>Rome</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Santoro, M Gabriella" sort="Santoro, M Gabriella" uniqKey="Santoro M" first="M. Gabriella" last="Santoro">M. Gabriella Santoro</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biology, University of Rome Tor Vergata</s1><s2>Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">07-0058292</idno><date when="2006">2006</date><idno type="stanalyst">PASCAL 07-0058292 INIST</idno><idno type="RBID">Pascal:07-0058292</idno><idno type="wicri:Area/PascalFrancis/Corpus">000421</idno><idno type="wicri:Area/PascalFrancis/Curation">000568</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Indomethacin has a potent antiviral activity against SARS coronavirus</title><author><name sortKey="Amici, Carla" sort="Amici, Carla" uniqKey="Amici C" first="Carla" last="Amici">Carla Amici</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biology, University of Rome Tor Vergata</s1><s2>Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Di Caro, Antonino" sort="Di Caro, Antonino" uniqKey="Di Caro A" first="Antonino" last="Di Caro">Antonino Di Caro</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Virology, National Institute for Infectious Diseases 'L. Spallanzani'</s1><s2>Rome</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Ciucci, Alessandra" sort="Ciucci, Alessandra" uniqKey="Ciucci A" first="Alessandra" last="Ciucci">Alessandra Ciucci</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biology, University of Rome Tor Vergata</s1><s2>Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Chiappa, Lucia" sort="Chiappa, Lucia" uniqKey="Chiappa L" first="Lucia" last="Chiappa">Lucia Chiappa</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biology, University of Rome Tor Vergata</s1><s2>Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Castilletti, Concetta" sort="Castilletti, Concetta" uniqKey="Castilletti C" first="Concetta" last="Castilletti">Concetta Castilletti</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Virology, National Institute for Infectious Diseases 'L. Spallanzani'</s1><s2>Rome</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Martella, Vito" sort="Martella, Vito" uniqKey="Martella V" first="Vito" last="Martella">Vito Martella</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Faculty of Veterinary Medicine, University of Bari</s1><s2>Bari</s2><s3>ITA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Decaro, Nicola" sort="Decaro, Nicola" uniqKey="Decaro N" first="Nicola" last="Decaro">Nicola Decaro</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Faculty of Veterinary Medicine, University of Bari</s1><s2>Bari</s2><s3>ITA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Buonavoglia, Canio" sort="Buonavoglia, Canio" uniqKey="Buonavoglia C" first="Canio" last="Buonavoglia">Canio Buonavoglia</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Faculty of Veterinary Medicine, University of Bari</s1><s2>Bari</s2><s3>ITA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Capobianchi, Maria R" sort="Capobianchi, Maria R" uniqKey="Capobianchi M" first="Maria R." last="Capobianchi">Maria R. Capobianchi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Laboratory of Virology, National Institute for Infectious Diseases 'L. Spallanzani'</s1><s2>Rome</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author><author><name sortKey="Santoro, M Gabriella" sort="Santoro, M Gabriella" uniqKey="Santoro M" first="M. Gabriella" last="Santoro">M. Gabriella Santoro</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biology, University of Rome Tor Vergata</s1><s2>Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Italie</country></affiliation></author></analytic><series><title level="j" type="main">Antiviral therapy : (London)</title><title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title><idno type="ISSN">1359-6535</idno><imprint><date when="2006">2006</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Antiviral therapy : (London)</title><title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title><idno type="ISSN">1359-6535</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral</term><term>Indometacin</term><term>Non steroidal antiinflammatory agent</term><term>Severe acute respiratory syndrome virus</term><term>Tocolytic</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Indométacine</term><term>Antiviral</term><term>Virus syndrome respiratoire aigu sévère</term><term>Antiinflammatoire non stéroïde</term><term>Tocolytique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. Objectives: Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication. Methods: Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID<sub>50</sub>, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after <sup>35</sup>S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO). Results: Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs. Conclusions: The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>1359-6535</s0></fA01><fA03 i2="1"><s0>Antivir. ther. : (Lond.)</s0></fA03><fA05><s2>11</s2></fA05><fA06><s2>8</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Indomethacin has a potent antiviral activity against SARS coronavirus</s1></fA08><fA11 i1="01" i2="1"><s1>AMICI (Carla)</s1></fA11><fA11 i1="02" i2="1"><s1>DI CARO (Antonino)</s1></fA11><fA11 i1="03" i2="1"><s1>CIUCCI (Alessandra)</s1></fA11><fA11 i1="04" i2="1"><s1>CHIAPPA (Lucia)</s1></fA11><fA11 i1="05" i2="1"><s1>CASTILLETTI (Concetta)</s1></fA11><fA11 i1="06" i2="1"><s1>MARTELLA (Vito)</s1></fA11><fA11 i1="07" i2="1"><s1>DECARO (Nicola)</s1></fA11><fA11 i1="08" i2="1"><s1>BUONAVOGLIA (Canio)</s1></fA11><fA11 i1="09" i2="1"><s1>CAPOBIANCHI (Maria R.)</s1></fA11><fA11 i1="10" i2="1"><s1>SANTORO (M. Gabriella)</s1></fA11><fA14 i1="01"><s1>Department of Biology, University of Rome Tor Vergata</s1><s2>Rome</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="02"><s1>Laboratory of Virology, National Institute for Infectious Diseases 'L. Spallanzani'</s1><s2>Rome</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></fA14><fA14 i1="03"><s1>Faculty of Veterinary Medicine, University of Bari</s1><s2>Bari</s2><s3>ITA</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></fA14><fA20><s1>1021-1030</s1></fA20><fA21><s1>2006</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>27047</s2><s5>354000145200850080</s5></fA43><fA44><s0>0000</s0><s1>© 2007 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>23 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>07-0058292</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Antiviral therapy : (London)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Severe acute respiratory syndrome (SARS) is a newly emerging, highly transmissible and fatal disease caused by a previously unknown coronavirus (SARS-CoV). Existing in non-identified animal reservoirs, SARS-CoV continues to represent a threat to humans because there is no effective specific antiviral therapy for coronavirus infections. Objectives: Starting from the observation that cyclopentenone cyclooxygenase (COX) metabolites are active against several RNA viruses, we investigated the effect of the COX inhibitor indomethacin on coronavirus replication. Methods: Work involving infectious SARS-CoV was performed in biosafety level 3 facilities. SARS-CoV was grown in monkey VERO cells and human lung epithelial A549 cells, while canine coronavirus (CCoV) was grown in A72 canine cells. Antiviral activity was analysed by determining infective virus titres by TCID<sub>50</sub>, viral RNA synthesis by Northern blot analysis and real-time RT-PCR, and viral protein synthesis by SDS-PAGE analysis after <sup>35</sup>S-methionine-labelling. Antiviral efficacy in vivo was determined by evaluating virus titres in CCoV-infected dogs treated orally with 1 mg/kg body weight indomethacin (INDO). Results: Unexpectedly, we found that INDO has a potent direct antiviral activity against the coronaviruses SARS-CoV and CCoV. INDO does not affect coronavirus binding or entry into host cells, but acts by blocking viral RNA synthesis at cytoprotective doses. This effect is independent of cyclooxygenase inhibition. INDO's potent antiviral activity (>1,000-fold reduction in virus yield) was confirmed in vivo in CCoV-infected dogs. Conclusions: The results identify INDO as a potent inhibitor of coronavirus replication and suggest that, having both anti-inflammatory and antiviral activity, INDO could be beneficial in SARS therapy.</s0></fC01><fC02 i1="01" i2="X"><s0>002B02S05</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Indométacine</s0><s2>NK</s2><s2>FR</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Indometacin</s0><s2>NK</s2><s2>FR</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Indometacina</s0><s2>NK</s2><s2>FR</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Antiviral</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Antiviral</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Antiviral</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Virus syndrome respiratoire aigu sévère</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Severe acute respiratory syndrome virus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Antiinflammatoire non stéroïde</s0><s5>23</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Non steroidal antiinflammatory agent</s0><s5>23</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Antiinflamatorio no esteroide</s0><s5>23</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Tocolytique</s0><s5>24</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Tocolytic</s0><s5>24</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Tocolítico</s0><s5>24</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Indolacétique acide dérivé</s0><s2>FR</s2><s5>37</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Indoleacetic acid derivatives</s0><s2>FR</s2><s5>37</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Indolacético ácido derivado</s0><s2>FR</s2><s5>37</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0><s5>38</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Enzyme inhibitor</s0><s5>38</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Inhibidor enzima</s0><s5>38</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Prostaglandin-endoperoxide synthase</s0><s2>FE</s2><s5>39</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Prostaglandin-endoperoxide synthase</s0><s2>FE</s2><s5>39</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Prostaglandin-endoperoxide synthase</s0><s2>FE</s2><s5>39</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Oxidoreductases</s0><s2>FE</s2></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Oxidoreductases</s0><s2>FE</s2></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Oxidoreductases</s0><s2>FE</s2></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Enzima</s0><s2>FE</s2></fC07><fN21><s1>036</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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|wiki= Sante
|area= SrasV1
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|étape= Curation
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|texte= Indomethacin has a potent antiviral activity against SARS coronavirus
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